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Thomas Myron Coffman

James R. Clapp Distinguished Professor of Medicine, in the School of Medicine
Medicine, Nephrology
Duke Box 103015, Durham, NC 27710
Room 2018/MSBR2, 106 Research Drive, Durham, NC 27710

Selected Publications


Kidney Renin-Angiotensin System: Lost in a RAS Cascade.

Journal Article Hypertension · April 2024 Renin was discovered more than a century ago. Since then, the functions of the renin-angiotensin system in the kidney have been the focus of intensive research revealing its importance in regulation of renal physiology and in the pathogenesis of heart, vas ... Full text Link to item Cite

Urine tricarboxylic acid cycle metabolites and risk of end stage kidney disease in patients with type 2 diabetes.

Journal Article J Clin Endocrinol Metab · March 28, 2024 CONTEXT: Metabolites in tricarboxylic acid (TCA) pathway have pleiotropic functions. OBJECTIVE: To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease (CKD) progression in individuals with type 2 diabetes. DESI ... Full text Link to item Cite

TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation.

Journal Article J Clin Invest · March 14, 2024 In lung, thromboxane A2 (TXA2) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key ro ... Full text Link to item Cite

Heterogeneity by age and gender in the association of kidney function with mortality among patients with diabetes - analysis of diabetes registry in Singapore.

Journal Article BMC Nephrol · January 17, 2024 BACKGROUND: We aimed to explore the three-way interaction among age, gender, and kidney function on the risk of all-cause mortality and cardiovascular mortality among patients with type 2 diabetes (T2D). METHODS: In a retrospective cohort study, patients a ... Full text Link to item Cite

Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathy.

Journal Article Kidney Int · December 2023 Diabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops k ... Full text Link to item Cite

Artificial intelligence education: An evidence-based medicine approach for consumers, translators, and developers.

Journal Article Cell Rep Med · October 17, 2023 Current and future healthcare professionals are generally not trained to cope with the proliferation of artificial intelligence (AI) technology in healthcare. To design a curriculum that caters to variable baseline knowledge and skills, clinicians may be c ... Full text Link to item Cite

Oral Peroxisome Proliferator-Activated Receptor-α Agonist Enhances Corneal Nerve Regeneration in Patients With Type 2 Diabetes.

Journal Article Diabetes · July 1, 2023 Diabetic corneal neuropathy (DCN) is a common complication of diabetes. However, there are very limited therapeutic options. We investigated the effects of a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, fenofibrate, on 30 patients (60 eye ... Full text Link to item Cite

Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.

Journal Article Hypertension · March 2023 BACKGROUND: Ang II (angiotensin II) type 1 (AT1) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT1 receptor (AT1A and AT1B) of which knock-in Tagln-mediated smooth muscle AT1A silencing attenuated A ... Full text Link to item Cite

Soluble ACE2 Is Filtered into the Urine.

Journal Article Kidney360 · December 29, 2022 BACKGROUND: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, abundance of ACE2 is highest in the kidney, and it is also expressed in several e ... Full text Link to item Cite

Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

Journal Article Nat Commun · December 5, 2022 The kidney has large regenerative capacity, but this is compromised when kidney damage is excessive and renal tubular epithelial cells (TECs) undergo SNAI1-driven growth arrest. Here we investigate the role of IL11 in TECs, kidney injury and renal repair. ... Full text Link to item Cite

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Journal Article J Am Heart Assoc · October 4, 2022 Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids ... Full text Link to item Cite

A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport Syndrome.

Journal Article J Am Soc Nephrol · April 2022 BACKGROUND: Alport syndrome is a genetic disorder characterized by a defective glomerular basement membrane, tubulointerstitial fibrosis, inflammation, and progressive renal failure. IL-11 was recently implicated in fibrotic kidney disease, but its role in ... Full text Link to item Cite

Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments.

Journal Article Nat Genet · September 2021 The functional interpretation of genome-wide association studies (GWAS) is challenging due to the cell-type-dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTLs) for 659 microdissected ... Full text Link to item Cite

Vascular control of kidney epithelial transporters.

Journal Article Am J Physiol Renal Physiol · June 1, 2021 A major pathway in hypertension pathogenesis involves direct activation of ANG II type 1 (AT1) receptors in the kidney, stimulating Na+ reabsorption. AT1 receptors in tubular epithelia control expression and stimulation of Na+ transporters and channels. Re ... Full text Link to item Cite

Pathophysiology of Hypertension: The Mosaic Theory and Beyond.

Journal Article Circ Res · April 2, 2021 Dr Irvine Page proposed the Mosaic Theory of Hypertension in the 1940s advocating that hypertension is the result of many factors that interact to raise blood pressure and cause end-organ damage. Over the years, Dr Page modified his paradigm, and new conce ... Full text Link to item Cite

Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Journal Article Hypertension · February 2021 Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II i ... Full text Link to item Cite

Animal Models of Hypertension: A Scientific Statement From the American Heart Association.

Journal Article Hypertension · June 2019 Hypertension is the most common chronic disease in the world, yet the precise cause of elevated blood pressure often cannot be determined. Animal models have been useful for unraveling the pathogenesis of hypertension and for testing novel therapeutic stra ... Full text Link to item Cite

Association of Diabetic Retinopathy and Diabetic Kidney Disease With All-Cause and Cardiovascular Mortality in a Multiethnic Asian Population.

Journal Article JAMA Netw Open · March 1, 2019 IMPORTANCE: The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. OBJECTIVE: To examine the association of DR and DKD separately and jointly w ... Full text Link to item Cite

Complex Role for E-Prostanoid 4 Receptors in Hypertension.

Journal Article J Am Heart Assoc · February 19, 2019 Background Prostaglandin E2 ( PGE 2) is a major prostanoid with multiple actions that potentially affect blood pressure ( BP ). PGE 2 acts through 4 distinct E-prostanoid ( EP ) receptor isoforms: EP 1 to EP 4. The EP 4 receptor ( EP 4R) promotes PGE 2-dep ... Full text Open Access Link to item Cite

Kidney Renin-Angiotensin System: Lost in a RAS Cascade.

Journal Article Hypertension · April 2024 Renin was discovered more than a century ago. Since then, the functions of the renin-angiotensin system in the kidney have been the focus of intensive research revealing its importance in regulation of renal physiology and in the pathogenesis of heart, vas ... Full text Link to item Cite

Urine tricarboxylic acid cycle metabolites and risk of end stage kidney disease in patients with type 2 diabetes.

Journal Article J Clin Endocrinol Metab · March 28, 2024 CONTEXT: Metabolites in tricarboxylic acid (TCA) pathway have pleiotropic functions. OBJECTIVE: To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease (CKD) progression in individuals with type 2 diabetes. DESI ... Full text Link to item Cite

TXA2 attenuates allergic lung inflammation through regulation of Th2, Th9, and Treg differentiation.

Journal Article J Clin Invest · March 14, 2024 In lung, thromboxane A2 (TXA2) activates the TP receptor to induce proinflammatory and bronchoconstrictor effects. Thus, TP receptor antagonists and TXA2 synthase inhibitors have been tested as potential asthma therapeutics in humans. Th9 cells play key ro ... Full text Link to item Cite

Heterogeneity by age and gender in the association of kidney function with mortality among patients with diabetes - analysis of diabetes registry in Singapore.

Journal Article BMC Nephrol · January 17, 2024 BACKGROUND: We aimed to explore the three-way interaction among age, gender, and kidney function on the risk of all-cause mortality and cardiovascular mortality among patients with type 2 diabetes (T2D). METHODS: In a retrospective cohort study, patients a ... Full text Link to item Cite

Abnormal lactate metabolism is linked to albuminuria and kidney injury in diabetic nephropathy.

Journal Article Kidney Int · December 2023 Diabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops k ... Full text Link to item Cite

Artificial intelligence education: An evidence-based medicine approach for consumers, translators, and developers.

Journal Article Cell Rep Med · October 17, 2023 Current and future healthcare professionals are generally not trained to cope with the proliferation of artificial intelligence (AI) technology in healthcare. To design a curriculum that caters to variable baseline knowledge and skills, clinicians may be c ... Full text Link to item Cite

Oral Peroxisome Proliferator-Activated Receptor-α Agonist Enhances Corneal Nerve Regeneration in Patients With Type 2 Diabetes.

Journal Article Diabetes · July 1, 2023 Diabetic corneal neuropathy (DCN) is a common complication of diabetes. However, there are very limited therapeutic options. We investigated the effects of a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, fenofibrate, on 30 patients (60 eye ... Full text Link to item Cite

Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II.

Journal Article Hypertension · March 2023 BACKGROUND: Ang II (angiotensin II) type 1 (AT1) receptors play a critical role in cardiovascular diseases such as hypertension. Rodents have 2 types of AT1 receptor (AT1A and AT1B) of which knock-in Tagln-mediated smooth muscle AT1A silencing attenuated A ... Full text Link to item Cite

Soluble ACE2 Is Filtered into the Urine.

Journal Article Kidney360 · December 29, 2022 BACKGROUND: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, abundance of ACE2 is highest in the kidney, and it is also expressed in several e ... Full text Link to item Cite

Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

Journal Article Nat Commun · December 5, 2022 The kidney has large regenerative capacity, but this is compromised when kidney damage is excessive and renal tubular epithelial cells (TECs) undergo SNAI1-driven growth arrest. Here we investigate the role of IL11 in TECs, kidney injury and renal repair. ... Full text Link to item Cite

Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages.

Journal Article J Am Heart Assoc · October 4, 2022 Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti-inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids ... Full text Link to item Cite

A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport Syndrome.

Journal Article J Am Soc Nephrol · April 2022 BACKGROUND: Alport syndrome is a genetic disorder characterized by a defective glomerular basement membrane, tubulointerstitial fibrosis, inflammation, and progressive renal failure. IL-11 was recently implicated in fibrotic kidney disease, but its role in ... Full text Link to item Cite

Mapping the genetic architecture of human traits to cell types in the kidney identifies mechanisms of disease and potential treatments.

Journal Article Nat Genet · September 2021 The functional interpretation of genome-wide association studies (GWAS) is challenging due to the cell-type-dependent influences of genetic variants. Here, we generated comprehensive maps of expression quantitative trait loci (eQTLs) for 659 microdissected ... Full text Link to item Cite

Vascular control of kidney epithelial transporters.

Journal Article Am J Physiol Renal Physiol · June 1, 2021 A major pathway in hypertension pathogenesis involves direct activation of ANG II type 1 (AT1) receptors in the kidney, stimulating Na+ reabsorption. AT1 receptors in tubular epithelia control expression and stimulation of Na+ transporters and channels. Re ... Full text Link to item Cite

Pathophysiology of Hypertension: The Mosaic Theory and Beyond.

Journal Article Circ Res · April 2, 2021 Dr Irvine Page proposed the Mosaic Theory of Hypertension in the 1940s advocating that hypertension is the result of many factors that interact to raise blood pressure and cause end-organ damage. Over the years, Dr Page modified his paradigm, and new conce ... Full text Link to item Cite

Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Journal Article Hypertension · February 2021 Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II i ... Full text Link to item Cite

Animal Models of Hypertension: A Scientific Statement From the American Heart Association.

Journal Article Hypertension · June 2019 Hypertension is the most common chronic disease in the world, yet the precise cause of elevated blood pressure often cannot be determined. Animal models have been useful for unraveling the pathogenesis of hypertension and for testing novel therapeutic stra ... Full text Link to item Cite

Association of Diabetic Retinopathy and Diabetic Kidney Disease With All-Cause and Cardiovascular Mortality in a Multiethnic Asian Population.

Journal Article JAMA Netw Open · March 1, 2019 IMPORTANCE: The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. OBJECTIVE: To examine the association of DR and DKD separately and jointly w ... Full text Link to item Cite

Complex Role for E-Prostanoid 4 Receptors in Hypertension.

Journal Article J Am Heart Assoc · February 19, 2019 Background Prostaglandin E2 ( PGE 2) is a major prostanoid with multiple actions that potentially affect blood pressure ( BP ). PGE 2 acts through 4 distinct E-prostanoid ( EP ) receptor isoforms: EP 1 to EP 4. The EP 4 receptor ( EP 4R) promotes PGE 2-dep ... Full text Open Access Link to item Cite

Inflammation and Immunity Pathways Regulate Genetic Susceptibility to Diabetic Nephropathy.

Journal Article Diabetes · October 2018 Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide, but its molecular pathogenesis is not well defined, and there are no specific treatments. In humans, there is a strong genetic component determining susceptibility to DN. Ho ... Full text Link to item Cite

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.

Journal Article Physiol Rev · July 1, 2018 The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (AT1R) is believed to mediate most funct ... Full text Link to item Cite

Angiotensin II Short-Loop Feedback: Is There a Role of Ang II for the Regulation of the Renin System In Vivo?

Journal Article Hypertension · June 2018 The activity of the renin-angiotensin-aldosterone system is triggered by the release of the protease renin from the kidneys, which in turn is controlled in the sense of negative feedback loops. It is widely assumed that Ang II (angiotensin II) directly inh ... Full text Link to item Cite

Modelling diabetic nephropathy in mice.

Journal Article Nat Rev Nephrol · January 2018 Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A bar ... Full text Link to item Cite

Oliver Smithies: A Remembrance.

Journal Article Hypertension · July 2017 Full text Link to item Cite

Resistance to hypertension mediated by intercalated cells of the collecting duct.

Journal Article JCI Insight · April 6, 2017 The renal collecting duct (CD), as the terminal segment of the nephron, is responsible for the final adjustments to the amount of sodium excreted in urine. While angiotensin II modulates reabsorptive functions of the CD, the contribution of these actions t ... Full text Link to item Cite

In the Wake of Systolic Blood Pressure Intervention Trial: New Targets for Improving Hypertension Management in Chronic Kidney Disease?

Journal Article Nephron · 2017 Systolic Blood Pressure Intervention Trial (SPRINT) was a multicenter randomized controlled trial showing the significant benefit of intensive reduction of blood pressure to a target of 120 mm Hg in individuals with hypertension and elevated cardiovascular ... Full text Link to item Cite

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development.

Journal Article Am J Physiol Renal Physiol · September 1, 2016 Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF ... Full text Link to item Cite

Impact of Angiotensin Type 1A Receptors in Principal Cells of the Collecting Duct on Blood Pressure and Hypertension.

Journal Article Hypertension · June 2016 The main actions of the renin-angiotensin system to control blood pressure (BP) are mediated by the angiotensin type 1 receptors (AT1Rs). The major murine AT1R isoform, AT1AR, is expressed throughout the nephron, including the collecting duct in both princ ... Full text Link to item Cite

Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

Conference Hypertension · May 2016 We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors in Agtr1a(-/-) and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in dr ... Full text Link to item Cite

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

Journal Article J Am Soc Nephrol · December 2015 Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, ... Full text Link to item Cite

Skin tight: macrophage-specific COX-2 induction links salt handling in kidney and skin.

Journal Article J Clin Invest · November 2, 2015 The relationship between dietary salt intake and the associated risk of hypertension and cardiovascular disease is an important public health concern. In this issue of the JCI, a study by Zhang and associates shows that consumption of a high-sodium diet in ... Full text Link to item Cite

Tubulovascular cross-talk by vascular endothelial growth factor a maintains peritubular microvasculature in kidney.

Journal Article J Am Soc Nephrol · May 2015 Vascular endothelial growth factor A (VEGFA) production by podocytes is critical for glomerular endothelial health. VEGFA is also expressed in tubular epithelial cells in kidney; however, its physiologic role in the tubule has not been established. Using t ... Full text Link to item Cite

Salt restriction leads to activation of adult renal mesenchymal stromal cell-like cells via prostaglandin E2 and E-prostanoid receptor 4.

Journal Article Hypertension · May 2015 Despite the importance of juxtaglomerular cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchy ... Full text Link to item Cite

Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis.

Journal Article Mol Metab · April 2015 OBJECTIVE: Elevations in brain angiotensin-II cause increased energy expenditure and a lean phenotype. Interestingly, the metabolic effects of increased brain angiotensin-II mimic the actions of leptin, suggesting an interaction between the two systems. He ... Full text Link to item Cite

AT1 Angiotensin receptors-vascular and renal epithelial pathways for blood pressure regulation.

Journal Article Curr Opin Pharmacol · April 2015 Angiotensin type 1 (AT1) receptors are key effector elements of the renin-angiotensin system, mediating virtually all of the classical physiological actions of angiotensin II. Pharmacological blockade of the AT1 receptor effectively lowers blood pressure i ... Full text Link to item Cite

Angiotensin type 1a receptors in the forebrain subfornical organ facilitate leptin-induced weight loss through brown adipose tissue thermogenesis

Journal Article Molecular Metabolism · April 1, 2015 Objective: Elevations in brain angiotensin-II cause increased energy expenditure and a lean phenotype. Interestingly, the metabolic effects of increased brain angiotensin-II mimic the actions of leptin, suggesting an interaction between the two systems. He ... Full text Cite

The effects of Ins2(Akita) diabetes and chronic angiotensin II infusion on cystometric properties in mice.

Journal Article Neurourol Urodyn · January 2015 AIMS: Diabetes is associated with both dysfunction of the lower urinary tract (LUT) and overactivity of the renin-angiotensin system (RAS). Although it is well known that the RAS affects normal LUT function, very little is known about RAS effects on the di ... Full text Link to item Cite

A conversation with Oliver Smithies.

Journal Article Annu Rev Physiol · 2015 Professor Oliver Smithies is the Weatherspoon Eminent Distinguished Professor of Pathology and Laboratory Medicine at the University of North Carolina, Chapel Hill. Along with Mario Capecchi and Martin Evans, Oliver was awarded the Nobel Prize in Medicine ... Full text Link to item Cite

Classical Renin-Angiotensin system in kidney physiology.

Journal Article Compr Physiol · July 2014 The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardiovascular system and the central nervous system. Along with its impact o ... Full text Link to item Cite

The inextricable role of the kidney in hypertension.

Journal Article J Clin Invest · June 2014 An essential link between the kidney and blood pressure control has long been known. Here, we review evidence supporting the premise that an impaired capacity of the kidney to excrete sodium in response to elevated blood pressure is a major contributor to ... Full text Link to item Cite

Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

Journal Article NMR Biomed · December 2013 Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of foca ... Full text Link to item Cite

The effects of Ins2(Akita) diabetes and chronic angiotensin II infusion on cystometric properties in mice.

Journal Article Neurourol Urodyn · October 28, 2013 AIMS: Diabetes is associated with both dysfunction of the lower urinary tract (LUT) and overactivity of the renin-angiotensin system (RAS). Although it is well known that the RAS affects normal LUT function, very little is known about RAS effects on the di ... Full text Link to item Cite

The Renin-Angiotensin System

Journal Article · September 12, 2013 Full text Cite

Diabetic nephropathy: a national dialogue.

Journal Article Clin J Am Soc Nephrol · September 2013 The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue (KRND) asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function a ... Full text Link to item Cite

Determination of an angiotensin II-regulated proteome in primary human kidney cells by stable isotope labeling of amino acids in cell culture (SILAC).

Journal Article J Biol Chem · August 23, 2013 Angiotensin II (AngII), the major effector of the renin-angiotensin system, mediates kidney disease progression by signaling through the AT-1 receptor (AT-1R), but there are no specific measures of renal AngII activity. Accordingly, we sought to define an ... Full text Link to item Cite

Cells of renin lineage are progenitors of podocytes and parietal epithelial cells in experimental glomerular disease.

Journal Article Am J Pathol · August 2013 Glomerular injury leads to podocyte loss, a process directly underlying progressive glomerular scarring and decline of kidney function. The inherent repair process is limited by the inability of podocytes to regenerate. Cells of renin lineage residing alon ... Full text Link to item Cite

Control of electrolyte balance through ubiquitination.

Journal Article Proc Natl Acad Sci U S A · May 7, 2013 Full text Link to item Cite

A trip to inner space: insights into salt balance from cosmonauts.

Journal Article Cell Metab · January 8, 2013 The epidemiological association between high salt intake and hypertension is well established. However, in most patients, the specific defect causing salt-dependent hypertension cannot be discerned. In this issue of Cell Metabolism, Rakova and associates u ... Full text Link to item Cite

Thromboxane receptors in smooth muscle promote hypertension, vascular remodeling, and sudden death.

Journal Article Hypertension · January 2013 The prostanoid thromboxane A2 has been implicated to contribute to the pathogenesis of many cardiovascular diseases, including hypertension. To study the role of vascular thromboxane-prostanoid (TP) receptors in blood pressure regulation, we generated mice ... Full text Link to item Cite

Lack of specificity of commercial antibodies leads to misidentification of angiotensin type 1 receptor protein.

Journal Article Hypertension · January 2013 The angiotensin II type 1 receptor (AT(1)R) mediates most hypertensive actions of angiotensin II. To understand the molecular regulation of the AT(1)R in normal physiology and pathophysiology, methods for sensitive and specific detection of AT(1)R protein ... Full text Link to item Cite

The Renin-Angiotensin System

Chapter · December 31, 2012 Full text Cite

A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

Journal Article Circ Res · June 8, 2012 RATIONALE: Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) rec ... Full text Link to item Cite

Recent advances involving the renin-angiotensin system.

Journal Article Exp Cell Res · May 15, 2012 The renin-angiotensin system (RAS) exercises fundamental control over sodium and water handling in the kidney. Accordingly, dysregulation of the RAS leads to blood pressure elevation with ensuing renal and cardiovascular damage. Recent studies have reveale ... Full text Link to item Cite

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors.

Journal Article Hypertens Res · May 2012 The renin-angiotensin system (RAS) has a vital role in regulating the cardiovascular system. The primary effector of the RAS is the octapeptide angiotensin (Ang) II, a potent regulator of blood pressure and water homeostasis. Ang II mediates its functions ... Full text Link to item Cite

The kidney and hypertension: lessons from mouse models.

Journal Article Can J Cardiol · May 2012 The pathogenesis of hypertension is multi-factorial, involving many of the systems contributing to blood pressure homeostasis including the vasculature, kidneys, central, and sympathetic nervous systems, along with various hormonal regulators. However, ove ... Full text Link to item Cite

The kidney and hypertension: novel insights from transgenic models.

Journal Article Curr Opin Nephrol Hypertens · March 2012 PURPOSE OF REVIEW: Despite decades of study, the pathogenesis of essential hypertension remains obscure, but the kidney appears to play a central role. Technology for manipulation of the mouse genome has been immensely valuable in dissecting pathways invol ... Full text Link to item Cite

Allergic inflammation induces a persistent mechanistic switch in thromboxane-mediated airway constriction in the mouse.

Journal Article Am J Physiol Lung Cell Mol Physiol · January 1, 2012 Actions of thromboxane (TXA(2)) to alter airway resistance were first identified over 25 years ago. However, the mechanism underlying this physiological response has remained largely undefined. Here we address this question using a novel panel of mice in w ... Full text Link to item Cite

Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin.

Journal Article Am J Physiol Renal Physiol · December 2011 Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl(-) absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whet ... Full text Link to item Cite

AT1 receptors in the collecting duct directly modulate the concentration of urine.

Journal Article J Am Soc Nephrol · December 2011 Mice lacking AT(1) angiotensin receptors have an impaired capacity to concentrate the urine, but the underlying mechanism is unknown. To determine whether direct actions of AT(1) receptors in epithelial cells of the collecting duct regulate water reabsorpt ... Full text Link to item Cite

Under pressure: the search for the essential mechanisms of hypertension.

Journal Article Nat Med · November 7, 2011 High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health because of its associated complications. Despite the high prevalence of essential hypertension and years of research, the basic causes remain obscure ... Full text Link to item Cite

Role of AT₁ receptor-mediated salt retention in angiotensin II-dependent hypertension.

Journal Article Am J Physiol Renal Physiol · November 2011 Activation of type 1 angiotensin II (AT(1)) receptors in the kidney promotes blood pressure elevation and target organ damage, but whether renal AT(1) receptors influence the level of hypertension by stimulating sodium retention or by raising systemic vasc ... Full text Link to item Cite

A major role for the EP4 receptor in regulation of renin.

Journal Article Am J Physiol Renal Physiol · November 2011 Prostaglandins have been implicated as paracrine regulators of renin secretion, but the specific pathways and receptor(s) carrying out these functions have not been fully elucidated. To examine the contributions of prostanoid synthetic pathways and recepto ... Full text Link to item Cite

Thromboxane receptor signalling in renal ischemia reperfusion injury.

Journal Article Free Radic Res · June 2011 F(2)-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F(2)-isoprostanes are biologically active compounds that signal through the thromboxane A(2) (TP) receptor; infu ... Full text Link to item Cite

AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure.

Journal Article Cell Metab · April 6, 2011 Hypertension affects more than 1.5 billion people worldwide but the precise cause of elevated blood pressure (BP) cannot be determined in most affected individuals. Nonetheless, blockade of the renin-angiotensin system (RAS) lowers BP in the majority of pa ... Full text Link to item Cite

Angiotensin II type 1A receptors in vascular smooth muscle cells do not influence aortic remodeling in hypertension.

Journal Article Hypertension · March 2011 Vascular injury and remodeling are common pathological sequelae of hypertension. Previous studies have suggested that the renin-angiotensin system acting through the type 1 angiotensin II (AT(1)) receptor promotes vascular pathology in hypertension. To stu ... Full text Link to item Cite

B lymphocytes differentially influence acute and chronic allograft rejection in mice.

Journal Article J Immunol · February 15, 2011 The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD1 ... Full text Link to item Cite

New insights into angiotensin receptor actions: from blood pressure to aging.

Journal Article Curr Opin Nephrol Hypertens · January 2011 PURPOSE OF REVIEW: The renin-angiotensin system (RAS) is critical for cardiovascular control, impacting normal physiology and disease pathogenesis. Although several biologically active peptides are generated by this system, its major actions are mediated b ... Full text Link to item Cite

Gene expression profiles linked to AT1 angiotensin receptors in the kidney.

Journal Article Physiol Genomics · November 15, 2010 To characterize gene expression networks linked to AT(1) angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT(1A) receptor-deficient mice (KOs) at baseline and after 2 days of ... Full text Link to item Cite

Renal actions of RGS2 control blood pressure.

Journal Article J Am Soc Nephrol · November 2010 G protein-coupled receptors (GPCRs) have key roles in cardiovascular regulation and are important targets for the treatment of hypertension. GTPase-activating proteins, such as RGS2, modulate downstream signaling by GPCRs. RGS2 displays regulatory selectiv ... Full text Link to item Cite

An IRKO in the Podo: impaired insulin signaling in podocytes and the pathogenesis of diabetic nephropathy.

Journal Article Cell Metab · October 6, 2010 Despite its high prevalence, the mechanisms causing diabetic kidney disease remain poorly understood. In this issue of Cell Metabolism, Welsh et al. (2010) show that elimination of insulin receptors from the glomerular podocyte, a cell that is central to t ... Full text Link to item Cite

Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts.

Journal Article Cardiovasc Res · June 1, 2010 AIMS: Our aim was to determine the contribution of the three angiotensin (Ang) II receptor subtypes (AT(1a), AT(1b), AT(2)) to coronary responsiveness, cardiac histopathology, and tissue Ang II levels using mice deficient for one, two, or all three Ang II ... Full text Link to item Cite

Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice.

Journal Article Am J Physiol Renal Physiol · March 2010 Featured Publication Previous studies have shown that Akita mice bearing the Ins2(+/C96Y) mutation have significant advantages as a type I diabetes platform for developing models of diabetic nephropathy (DN; Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Am J Physio ... Full text Link to item Cite

Angiotensin II promotes development of the renal microcirculation through AT1 receptors.

Journal Article J Am Soc Nephrol · March 2010 Pharmacologic or genetic deletion of components of the renin-angiotensin system leads to postnatal kidney injury, but the roles of these components in kidney development are unknown. To test the hypothesis that angiotensin II supports angiogenesis during p ... Full text Link to item Cite

The impact of microsomal prostaglandin e synthase 1 on blood pressure is determined by genetic background.

Journal Article Hypertension · February 2010 Featured Publication Prostaglandin (PG)E(2) has multiple actions that may affect blood pressure. It is synthesized from arachidonic acid by the sequential actions of phospholipases, cyclooxygenases, and PGE synthases. Although microsomal PGE synthase (mPGES)1 is the only genet ... Full text Link to item Cite

Mouse models of diabetic nephropathy.

Journal Article J Am Soc Nephrol · December 2009 Diabetic nephropathy is a major cause of ESRD worldwide. Despite its prevalence, a lack of reliable animal models that mimic human disease has delayed the identification of specific factors that cause or predict diabetic nephropathy. The Animal Models of D ... Full text Link to item Cite

Developmental renin expression in mice with a defective renin-angiotensin system.

Journal Article Am J Physiol Renal Physiol · November 2009 During nephrogenesis, renin expression shifts from the vessel walls of interlobular arteries to the terminal portions of afferent arterioles in a wavelike pattern. Since the mechanisms responsible for the developmental deactivation of renin expression are ... Full text Link to item Cite

Aldosterone-induced activation of signaling pathways requires activity of angiotensin type 1a receptors.

Journal Article Circ Res · October 23, 2009 RATIONALE: Aldosterone has been shown to induce vascular damage, endothelial dysfunction, and myocardial fibrosis, which depend in part on activation of angiotensin II (Ang II)-mediated pathways. However, mechanisms underlying crosstalk between Ang II type ... Full text Link to item Cite

Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression.

Journal Article Hypertension · September 2009 Featured Publication Drugs and antibodies that interrupt vascular endothelial growth factor (VEGF) signaling pathways improve outcomes in patients with a variety of cancers by inhibiting tumor angiogenesis. A major adverse effect of these treatments is hypertension, suggesting ... Full text Link to item Cite

Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis.

Journal Article J Clin Invest · April 2009 Featured Publication Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we genera ... Full text Link to item Cite

Disruption of the Ang II type 1 receptor promotes longevity in mice.

Journal Article J Clin Invest · March 2009 Featured Publication The renin-angiotensin system plays a role in the etiology of hypertension and the pathophysiology of cardiac and renal diseases in humans. Ang II is the central product of this system and is involved in regulating immune responses, inflammation, cell growt ... Full text Link to item Cite

Primer on Kidney Diseases

Book · January 1, 2009 This official publication of the National Kidney Foundation (NKF) covers all aspects of adult and pediatric kidney diseases and is ideal for nephrologists and non-nephrologists alike. The full-color design, high-quality photographs, and outstanding graphs ... Cite

AT1 ANGIOTENSIN RECEPTORS IN THE KIDNEY: A KEY TO BLOOD PRESSURE CONTROL

Conference JOURNAL OF PHYSIOLOGICAL SCIENCES · January 1, 2009 Link to item Cite

The Renin-Angiotensin System

Journal Article · December 1, 2008 Full text Cite

Increased blood pressure in mice lacking cytochrome P450 2J5.

Journal Article FASEB J · December 2008 The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical functions, including metabolism of arachidonic acid and steroid hormones. Mouse CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic acids (EETs), modu ... Full text Link to item Cite

Stressed-out podocytes in diabetes?

Journal Article J Am Soc Nephrol · November 2008 Full text Link to item Cite

In hypertension, the kidney breaks your heart.

Journal Article Curr Cardiol Rep · November 2008 The renin-angiotensin system (RAS) is a master regulator of blood pressure and fluid homeostasis. Because RAS components are expressed in several tissues that may influence blood pressure, studies using conventional gene targeting to globally interrupt the ... Full text Link to item Cite

A role for the thromboxane receptor in L-NAME hypertension.

Journal Article Am J Physiol Renal Physiol · October 2008 Actions of the lipid mediator thromboxane (Tx) A2 acting through the TP receptor contribute to the pathogenesis of cardiovascular disease. To further explore the role of TxA2 in hypertension, we examined the consequences of deficiency of the TP receptor on ... Full text Link to item Cite

Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension.

Journal Article Am J Physiol Renal Physiol · August 2008 Activation of the renin-angiotensin system contributes to the progression of chronic kidney disease. Based on the known cellular effects of ANG II to promote inflammation, we posited that stimulation of lymphocyte responses by ANG II might contribute to th ... Full text Link to item Cite

Cardiovascular phenotype of mice lacking all three subtypes of angiotensin II receptors.

Journal Article FASEB J · August 2008 Angiotensin II activates two distinct receptors, the angiotensin II receptors type 1 (AT(1)) and type 2 (AT(2)). In rodents, two AT(1) subtypes were identified (AT(1a) and AT(1b)). To determine receptor-specific functions and possible angiotensin II effect ... Full text Link to item Cite

Angiotensin-converting enzyme 2 gene targeting studies in mice: mixed messages.

Journal Article Exp Physiol · May 2008 As a major regulator of blood pressure homeostasis, the renin-angiotensin system (RAS) has been the subject of extensive scientific investigation. While the RAS was first discovered more than 100 years ago, several novel components of the system have been ... Full text Link to item Cite

Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle.

Journal Article J Biol Chem · April 25, 2008 In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smo ... Full text Link to item Cite

Kidney in hypertension: guyton redux.

Journal Article Hypertension · April 2008 Featured Publication Full text Link to item Cite

Targeting genes in the renin-angiotensin system.

Journal Article Curr Opin Nephrol Hypertens · January 2008 PURPOSE OF REVIEW: The renin-angiotensin system plays a key role in the regulation of blood pressure and fluid homeostasis. Owing to its critical contribution to blood pressure control, abnormalities of any component in this system can lead to hypertension ... Full text Link to item Cite

Role of microsomal prostaglandin E synthase 1 in the kidney.

Journal Article J Am Soc Nephrol · May 2007 Prostaglandin E(2) (PGE(2)) is one of the most ubiquitous prostanoids in the kidney, where it may influence a wide range of physiologic functions. PGE(2) is generated through enzymatic metabolism of prostanoid endoperoxides by specific PGE synthases (PGES) ... Full text Link to item Cite

Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection.

Journal Article J Exp Med · April 16, 2007 Chagas' disease is caused by infection with the parasite Trypanosoma cruzi. We report that infected, but not uninfected, human endothelial cells (ECs) released thromboxane A(2) (TXA(2)). Physical chromatography and liquid chromatography-tandem mass spectro ... Full text Link to item Cite

The renin-angiotensin system: it's all in your head.

Journal Article J Clin Invest · April 2007 Components of the renin-angiotensin system (RAS) are expressed in a number of areas in the brain involved in cardiovascular control. However, it has been difficult to link RAS actions in circumscribed brain regions to specific physiological functions. In a ... Full text Link to item Cite

In hypertension, the kidney rules.

Journal Article Curr Hypertens Rep · April 2007 The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Components of the RAS, including renin, angiotensin-converting enzyme (ACE), and angiotensin type 1 (AT1) receptors, are expressed throughout the body in ti ... Full text Link to item Cite

The renin-angiotensin system and diabetic nephropathy.

Journal Article Semin Nephrol · March 2007 Featured Publication The renin-angiotensin system (RAS) has key regulatory functions for blood pressure and fluid homeostasis. In addition, dysregulation of the system can have maladaptive effects to promote tissue injury in chronic diseases such as hypertension, heart failure ... Full text Link to item Cite

AT(1) receptors and control of blood pressure: the kidney and more..

Journal Article Trends Cardiovasc Med · January 2007 The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. The components of the RAS including renin, angiotensin-converting enzyme, and angiotensin receptors are expressed throughout the body in tissues that may im ... Full text Link to item Cite

Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney.

Journal Article Proc Natl Acad Sci U S A · November 21, 2006 Featured Publication Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenge ... Full text Link to item Cite

Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes.

Journal Article Proc Natl Acad Sci U S A · October 31, 2006 The G protein-coupled receptor kinases (GRKs) and beta-arrestins, families of molecules essential to the desensitization of G protein-dependent signaling via seven-transmembrane receptors (7TMRs), have been recently shown to also transduce G protein-indepe ... Full text Link to item Cite

A WNK in the kidney controls blood pressure.

Journal Article Nat Genet · October 2006 Featured Publication Full text Link to item Cite

Heparin binding EGF is necessary for vasospastic response to endothelin.

Journal Article FASEB J · September 2006 Endothelin-1 (ET-1), a powerful vasoconstrictor, is involved in vasospastic diseases such as coronary artery disease and subarachnoidal hemorrhage, as well as in renal and cardiovascular fibrotic remodeling. Transactivation of the epidermal growth factor r ... Full text Link to item Cite

Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice.

Journal Article J Clin Invest · August 2006 Featured Publication The carboxypeptidase ACE2 is a homologue of angiotensin-converting enzyme (ACE). To clarify the physiological roles of ACE2, we generated mice with targeted disruption of the Ace2 gene. ACE2-deficient mice were viable, fertile, and lacked any gross structu ... Full text Link to item Cite

ACE and ACE2 activity in diabetic mice.

Journal Article Diabetes · July 2006 ACE-related carboxypeptidase (ACE2) may counterbalance the angiotensin (ANG) II-promoting effects of ACE in tissues where both enzymes are found. Alterations in renal ACE and ACE2 expression have been described in experimental models of diabetes, but ACE2 ... Full text Link to item Cite

UCP-2 limits the development of angiotensin II-induced renal sclerosis

Conference NEPHROLOGY DIALYSIS TRANSPLANTATION · July 1, 2006 Link to item Cite

New mass spectrometric assay for angiotensin-converting enzyme 2 activity.

Journal Article Hypertension · May 2006 A novel assay was developed for evaluation of mouse angiotensin-converting enzyme (ACE) 2 and recombinant human ACE2 (rACE2) activity. Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (MS) with ProteinChip Array technolog ... Full text Link to item Cite

A new cardiac MASTer switch for the renin-angiotensin system.

Journal Article J Clin Invest · April 2006 The aspartyl protease renin was first isolated from the kidney by Tigerstedt more than a century ago. In the kidney, renin secretion is tightly linked to sodium intake and renal perfusion pressure, reflecting the important role of the renin-angiotensin sys ... Full text Link to item Cite

Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism.

Journal Article Am J Physiol Lung Cell Mol Physiol · March 2006 Thromboxane A2 (TXA2) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. In the airways, it has been postulated that TXA2 causes airway constriction by direct activat ... Full text Link to item Cite

Impact of genetic background on nephropathy in diabetic mice.

Journal Article Am J Physiol Renal Physiol · January 2006 With the goal of identifying optimal platforms for developing better models of diabetic nephropathy in mice, we compared renal effects of streptozotocin (STZ)-induced diabetes among five common inbred mouse strains (C57BL/6, MRL/Mp, BALB/c, DBA/2, and 129/ ... Full text Link to item Cite

Strategy for the development of a matched set of transport-competent, angiotensin receptor-deficient proximal tubule cell lines.

Journal Article In Vitro Cell Dev Biol Anim · 2006 In the proximal convoluted tubule (PCT) angiotensin II (Ang II) modulates fluid and electrolyte transport through at least two pharmacologically distinct receptor subtypes: AT(1) and AT(2). Development of cell lines that lack these receptors are potentiall ... Full text Link to item Cite

Activation of Galpha q-coupled signaling pathways in glomerular podocytes promotes renal injury.

Journal Article J Am Soc Nephrol · December 2005 The glomerular podocyte plays a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by activation of cell surface G protein-coupled receptors (GPCR). Studies suggest that podocytes express GPCR that ar ... Full text Link to item Cite

NSAIDs and cardiovascular risk - Reply [2]

Journal Article Cell Metabolism · December 1, 2005 Full text Cite

Th1 inflammatory response with altered expression of profibrotic and vasoactive mediators in AT1A and AT1B double-knockout mice.

Journal Article Am J Physiol Renal Physiol · October 2005 AT(1) double receptor (AT(1A) and AT(1B)) knockout mice have lower blood pressure, impaired growth, and develop early renal microvascular disease and tubulointerstitial injury. We hypothesized that there would be an increased expression of vasoactive, prof ... Full text Link to item Cite

Prostacyclin protects against elevated blood pressure and cardiac fibrosis.

Journal Article Cell Metab · September 2005 Featured Publication Specific inhibitors of COX-2 have been associated with increased risk for cardiovascular complications. These agents reduce prostacyclin (PGI2) without affecting production of thromboxane (Tx) A2. While this abnormal pattern of eicosanoid generation has be ... Full text Link to item Cite

Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor.

Journal Article Am J Physiol Heart Circ Physiol · August 2005 Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explo ... Full text Link to item Cite

Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.

Journal Article Clin Diagn Lab Immunol · August 2005 Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+) CD8(+) thymocyte ... Full text Link to item Cite

Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice.

Journal Article J Hepatol · August 2005 BACKGROUND/AIMS: Pharmacological blockade of the renin-angiotensin system (RAS) attenuates liver fibrogenesis in rats. Here, we provide genetic evidence implicating angiotensin type 1 (AT1) receptors in liver fibrogenesis. METHODS: Wild type (WT) and AT1a ... Full text Link to item Cite

COX-2-derived prostacyclin modulates vascular remodeling.

Journal Article Circ Res · June 24, 2005 Suppression of prostacyclin (PGI2) biosynthesis may explain the increased incidence of myocardial infarction and stroke which has been observed in placebo controlled trials of cyclooxygenase (COX)-2 inhibitors. Herein, we examine if COX-2-derived PGI2 migh ... Full text Link to item Cite

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system.

Journal Article J Clin Invest · April 2005 Featured Publication Angiotensin II, acting through type 1 angiotensin (AT(1)) receptors, has potent effects that alter renal excretory mechanisms. Control of sodium excretion by the kidney has been suggested to be the critical mechanism for blood pressure regulation by the re ... Full text Link to item Cite

Diabetic nephropathy: of mice and men.

Journal Article Adv Chronic Kidney Dis · April 2005 Accumulating evidence supports intrinsic genetic susceptibility as an important variable in the progression of diabetic nephropathy in people. Mice provide an experimental platform of unparalleled power for dissecting the genetics of mammalian diseases; ho ... Full text Link to item Cite

Mouse models of diabetic nephropathy.

Journal Article J Am Soc Nephrol · January 2005 Mice provide an experimental model of unparalleled flexibility for studying mammalian diseases. Inbred strains of mice exhibit substantial differences in their susceptibility to the renal complications of diabetes. Much remains to be established regarding ... Full text Link to item Cite

Targeted deletion of angiotensin II type 1A receptor does not protect mice from progressive nephropathy of overload proteinuria.

Journal Article J Am Soc Nephrol · October 2004 In experimental and human renal diseases, progression is limited by angiotensin-converting enzyme inhibitors. Whether renoprotection was due to their capacity of reducing proinflammatory and profibrotic effects of angiotensin II (Ang II) or limiting protei ... Full text Link to item Cite

Prostanoids and blood pressure: which way is up?

Journal Article J Clin Invest · September 2004 Members of the family of prostanoids, made up of prostaglandins and thromboxanes, are generated via COX-mediated metabolism of arachidonic acid. These lipid mediators exhibit wide-ranging biological actions that include regulating both vasomotor tone and r ... Full text Link to item Cite

Thromboxane receptor mediates renal vasoconstriction and contributes to acute renal failure in endotoxemic mice.

Journal Article J Am Soc Nephrol · September 2004 Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2 (TxA(2)) may mediate decreases of renal blood flow (RBF) and/or GFR associated with LPS-induced sepsis. This study tested whether TxA(2) receptor blockade, with the use of TxA(2 ... Full text Link to item Cite

A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice.

Journal Article Physiol Genomics · August 11, 2004 To understand the physiological role of angiotensin type 1 (AT(1)) receptors in the proximal tubule of the kidney, we generated a transgenic mouse line in which the major murine AT(1) receptor isoform, AT(1A), was expressed under the control of the P1 port ... Full text Link to item Cite

Exploring type I angiotensin (AT1) receptor functions through gene targeting.

Journal Article Acta Physiol Scand · August 2004 The renin-angiotensin system (RAS) modulates a diverse set of physiological processes including development, blood pressure, renal function and inflammation. The principal effector molecule of this system, angiotensin II, mediates most of these actions. Th ... Full text Link to item Cite

E-prostanoid-3 receptors mediate the proinflammatory actions of prostaglandin E2 in acute cutaneous inflammation.

Journal Article J Immunol · July 15, 2004 Featured Publication PGs are derived from arachidonic acid by PG-endoperoxide synthase (PTGS)-1 and PTGS2. Although enhanced levels of PGs are present during acute and chronic inflammation, a functional role for prostanoids in inflammation has not been clearly defined. Using a ... Full text Link to item Cite

Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2.

Journal Article Mol Cell Biol · May 2004 A family of orphan transporters has been discovered that are structurally related to the Na(+)-Cl(-)-dependent neurotransmitter transporters, including the dopamine transporter. One member of this family, the mouse XT2 gene, is predominantly expressed in t ... Full text Link to item Cite

Role for thromboxane receptors in angiotensin-II-induced hypertension.

Journal Article Hypertension · February 2004 To evaluate the role of thromboxane in hypertension and its complications, we studied mice with targeted disruption of the TXA2 receptor gene in an angiotensin-II-dependent model of hypertension. To determine whether genetic background might alter the phys ... Full text Link to item Cite

Modifier locus on mouse chromosome 3 for renal vascular pathology in AT1A receptor-deficiency.

Journal Article Hypertension · February 2004 We previously showed that the phenotype of mice with targeted disruption of the gene encoding the AT1A receptor (Agtr1a), the major murine AT1 receptor isoform, is strongly influenced by recessive genetic modifiers derived from the C57BL/6 or 129 inbred st ... Full text Link to item Cite

Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.

Journal Article J Immunol · December 15, 2003 Featured Publication Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a family of prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting COX, thereby reducing prostanoid synthesis. The efficacy of these agents in redu ... Full text Link to item Cite

Effector mechanisms in transplant rejection.

Journal Article Immunol Rev · December 2003 Antigens, provided by the allograft, trigger the activation and proliferation of allospecific T cells. As a consequence of this response, effector elements are generated that mediate graft injury and are responsible for the clinical manifestations of allog ... Full text Link to item Cite

Differential regulation of renin and Cox-2 expression in the renal cortex of C57Bl/6 mice.

Journal Article Pflugers Arch · November 2003 Based on the controversy about the relevance of cyclooxygenase-2 (Cox-2)-derived prostanoids from the macula densa for the control of the renin system, this study aimed to determine the interrelation between Cox-2 and renin expression in the mouse kidney. ... Full text Link to item Cite

Physiological impact of increased expression of the AT1 angiotensin receptor.

Journal Article Hypertension · October 2003 To test the effect of increased AT1 receptor expression on blood pressure, we used gene targeting to generate mouse lines with a tandem duplication of the AT1A receptor gene locus (Agtr1a) along with >10 kb of 5' flanking DNA. By successive breeding, we ge ... Full text Link to item Cite

The chemokine CX3CL1 regulates NK cell activity in vivo.

Journal Article Cell Immunol · October 2003 In vitro, chemokines can both activate and induce migration of NK cells. However, little is known about how chemokines influence NK cell activity in vivo. We studied the role of CX(3)CL1 and its receptor, CX(3)CR1, in modulating NK cell activity in an esta ... Full text Link to item Cite

Eicosanoids: lipid mediators of inflammation in transplantation.

Journal Article Springer Semin Immunopathol · September 2003 Featured Publication Eicosanoids are a family of lipid mediators derived from the metabolism of arachidonic acid. Eicosanoids, such as prostanoids and leukotrienes, have a wide range of biological actions including potent effects on inflammation and immunity. It has been almos ... Full text Link to item Cite

Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells.

Journal Article J Immunol · July 1, 2003 Featured Publication Coordinated rearrangements of the actin-myosin cytoskeleton facilitate early and late events in T cell activation and signal transduction. As many important features of cell shape rearrangement involve small GTP-binding proteins, we examined the contributi ... Full text Link to item Cite

Orthopaedic research and education foundation and industry.

Journal Article Clin Orthop Relat Res · July 2003 Members of orthopaedic industry commit a significant amount of funds each year to support research and education programs that are directly related to their product(s). In addition, industry supports organizations such as the Orthopaedic Research and Educa ... Full text Link to item Cite

The roles of alpha IIb beta 3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation.

Journal Article Blood · April 1, 2003 Collagen-induced activation of platelets in suspension leads to alpha(IIb)beta(3)-mediated outside-in signaling, granule release, thromboxane A2 (TxA2) production, and aggregation. Although much is known about collagen-induced platelet signaling, the roles ... Full text Link to item Cite

Renal segmental microvascular responses to ANG II in AT1A receptor null mice.

Journal Article Am J Physiol Renal Physiol · March 2003 The relative contributions of AT(1A) and AT(1B) receptors to afferent arteriolar autoregulatory capability and afferent and efferent arteriolar responses to ANG II are not known. Experiments were conducted in kidneys from wild-type (WT) and AT(1A)-/- mice ... Full text Link to item Cite

Renal segmental microvascular responses to ANG II in AT1A receptor null mice

Journal Article American Journal of Physiology - Renal Physiology · March 1, 2003 The relative contributions of AT1A and AT1B receptors to afferent arteriolar autoregulatory capability and afferent and efferent arteriolar responses to ANG II are not known. Experiments were conducted in kidneys from wild-type (WT) and AT1A-/- mice utiliz ... Cite

Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice.

Journal Article FASEB J · February 2003 Vascular remodeling and rearrangement of the extracellular matrix formation are among the major adaptive mechanisms in response to a chronic blood pressure increase. Vasoactive peptides, such as endothelin, participate in hypertension-associated vascular f ... Full text Link to item Cite

RGS2: a "turn-off" in hypertension.

Journal Article J Clin Invest · February 2003 Full text Link to item Cite

Prolonged survival of class II transactivator-deficient cardiac allografts.

Journal Article Transplantation · November 15, 2002 BACKGROUND: Major histocompatibility complex (MHC) antigenic complexes trigger allogeneic T-cell responses and allograft rejection. MHC class II and related antigen processing genes, such as invariant chain (Ii) and H2-DM accessory molecules, are controlle ... Full text Link to item Cite

Essential role of AT1A receptor in the development of 2K1C hypertension.

Journal Article Hypertension · November 2002 The aims of this study were to delineate the relative contribution of angiotensin II (ANG II) subtype 1A (AT1A) and 1B (AT1B) receptors to the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in mice, to examine if increased nitric oxide s ... Full text Link to item Cite

Receptors and signaling mechanisms required for prostaglandin E2-mediated regulation of mast cell degranulation and IL-6 production.

Journal Article J Immunol · October 15, 2002 Mast cells are implicated in the pathogenesis of a broad spectrum of immunological disorders. These cells release inflammatory mediators in response to a number of stimuli, including IgE-Ag complexes. The degranulation of mast cells is modified by PGs. To ... Full text Link to item Cite

Characterization of visual phenomena with the Array multifocal intraocular lens.

Journal Article J Cataract Refract Surg · July 2002 PURPOSE: To characterize the visual sensations reported after bilateral implantation of the Array multifocal intraocular lens (IOL) (Allergan Surgical) and evaluate the means to mitigate unwanted visual sensations. SETTING: Surgery centers in Kansas City, ... Full text Link to item Cite

Absence of donor MHC antigen expression ameliorates chronic kidney allograft rejection.

Journal Article Kidney Int · July 2002 BACKGROUND: In previous studies, we have demonstrated that a subset of mouse kidney allografts has prolonged survival without any immunosuppressive treatment. Chronic rejection (CR) develops in these long surviving grafts. The pathologic features of CR in ... Full text Link to item Cite

Role of prostacyclin in the cardiovascular response to thromboxane A2.

Journal Article Science · April 19, 2002 Thromboxane (Tx) A2 is a vasoconstrictor and platelet agonist. Aspirin affords cardioprotection through inhibition of TxA2 formation by platelet cyclooxygenase (COX-1). Prostacyclin (PGI2) is a vasodilator that inhibits platelet function. Here we show that ... Full text Link to item Cite

Another cystic mystery solved.

Journal Article Nat Genet · March 2002 Full text Link to item Cite

Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice.

Journal Article Hypertension · February 2002 The renal tubule transporters responsible for Na(+) and water transport along the nephron have been identified and cloned, permitting comprehensive analysis of transporter protein abundance changes in complex physiological models by using a "targeted prote ... Cite

Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice.

Journal Article Hypertension · February 2002 The renal tubule transporters responsible for Na(+) and water transport along the nephron have been identified and cloned, permitting comprehensive analysis of transporter protein abundance changes in complex physiological models by using a "targeted prote ... Full text Link to item Cite

Deficiency of COX-1 causes natriuresis and enhanced sensitivity to ACE inhibition.

Journal Article Kidney Int · December 2001 BACKGROUND: Prostanoid products of the cyclo-oxygenase (COX) pathway of arachidonic acid metabolism modulate blood pressure (BP) and sodium homeostasis. Conventional non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit both COX isoforms (COX-1 and ... Full text Link to item Cite

Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice.

Journal Article J Immunol · December 1, 2001 Acute renal allograft rejection is associated with alterations in renal arachidonic acid metabolism, including enhanced synthesis of leukotrienes (LTs). LTs, the products of the 5-lipoxygenase (5-LO) pathway, are potent lipid mediators with a broad range o ... Full text Link to item Cite

Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse.

Journal Article J Clin Invest · October 2001 Production of prostaglandin E(2) (PGE(2)) is enhanced during inflammation, and this lipid mediator can dramatically modulate immune responses. There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intrac ... Full text Link to item Cite

Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase.

Journal Article J Am Soc Nephrol · May 2001 Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene ... Full text Link to item Cite

Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors.

Journal Article Am J Physiol Regul Integr Comp Physiol · April 2001 The objective was to determine the central nervous system (CNS) responses to dehydration (c-Fos and vasopressin mRNA) in mice lacking the ANG AT(1a) receptor [ANG AT(1a) knockout (KO)]. Control and AT(1a) KO mice were dehydrated for 24 or 48 h. Baseline pl ... Full text Link to item Cite

Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation.

Journal Article J Clin Invest · March 2001 The importance of arachidonic acid metabolites (termed eicosanoids), particularly those derived from the COX-1 and COX-2 pathways (termed prostanoids), in platelet homeostasis has long been recognized. Thromboxane is a potent agonist, whereas prostacyclin ... Full text Link to item Cite

Review: Gene targeting studies of angiotensin II type 1 (AT1) receptors.

Journal Article J Renin Angiotensin Aldosterone Syst · March 2001 Full text Link to item Cite

The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.

Journal Article J Clin Invest · February 2001 The lipid mediator prostaglandin E2 (PGE2) has diverse biological activity in a variety of tissues. Four different receptor subtypes (EP1-4) mediate these wide-ranging effects. The EP-receptor subtypes differ in tissue distribution, ligand-binding affinity ... Full text Link to item Cite

Role of EP(2) and EP(3) PGE(2) receptors in control of murine renal hemodynamics.

Journal Article Am J Physiol Heart Circ Physiol · January 2001 The kidney plays a central role in long-term regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present ... Full text Link to item Cite

Circadian rhythms of activity and drinking in mice lacking angiotensin II 1A receptors.

Journal Article Physiol Behav · 2001 Angiotensin II (ANG II) type 1 receptors are found in the mouse suprachiasmatic nucleus (SCN), the site of the circadian pacemaker, but their significance for circadian timekeeping is unknown. We examined circadian rhythms of wheel running and drinking in ... Full text Link to item Cite

Role of EP2 and EP3 PGE2 receptors in control of murine renal hemodynamics

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · 2001 The kidney plays a central role in longterm regulation of arterial blood pressure and salt and water homeostasis. This is achieved in part by the local actions of paracrine and autacoid mediators such as the arachidonic acid-prostanoid system. The present ... Cite

A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.

Journal Article J Immunol · December 1, 2000 The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac is ... Full text Link to item Cite

Insights into the functions of type 1 (AT1) angiotensin II receptors provided by gene targeting.

Journal Article Trends Endocrinol Metab · September 2000 The renin-angiotensin system (RAS) has a wide range of actions in biological processes ranging from development and reproduction to cardiovascular and renal functions. Most of these actions are mediated by the octapeptide hormone angiotensin II. The identi ... Full text Link to item Cite

Angiotensin II Receptor Physiology Using Gene Targeting.

Journal Article News Physiol Sci · August 2000 The study of mice with targeted disruptions of angiotensin receptor genes has provided new insights into the roles of the individual receptor subtypes, i.e., AT(1A), AT(1B), and AT(2), in growth, development, and the regulation of blood pressure. ... Full text Link to item Cite

Angiotensin II: an immune costimulator?

Journal Article Am J Kidney Dis · August 2000 Full text Link to item Cite

H2-DMalpha(-/-) mice show the importance of major histocompatibility complex-bound peptide in cardiac allograft rejection.

Journal Article J Exp Med · July 3, 2000 The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMalpha(-/)- mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-bound, MHC clas ... Full text Link to item Cite

Divergent functions of angiotensin II receptor isoforms in the brain.

Journal Article J Clin Invest · July 2000 The renin-angiotensin system (RAS) plays a critical role in cardiovascular and fluid homeostasis. The major biologically active peptide of the RAS is angiotensin II, which acts through G protein-coupled receptors of two pharmacological classes, AT(1) and A ... Full text Link to item Cite

Cardiovascular responses to the isoprostanes iPF(2alpha)-III and iPE(2)-III are mediated via the thromboxane A(2) receptor in vivo.

Journal Article Circulation · June 20, 2000 BACKGROUND: Isoprostanes (iPs) are free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. Several iPs exert biological effects in vitro and may contribute to the functional consequences of oxidant stress. For example, ... Full text Link to item Cite

A role for leukotrienes in cyclosporine nephrotoxicity.

Journal Article Kidney Int · June 2000 BACKGROUND: Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis, and arteriolar hypertrophy. While the molecular mechanisms of CsA toxicity are not well characterized, ... Full text Link to item Cite

Altered intragraft immune responses and improved renal function in MHC class II-deficient mouse kidney allografts.

Journal Article Transplantation · May 27, 2000 BACKGROUND: During renal allograft rejection, expression of MHC class II antigens is up-regulated on the parenchymal cells of the kidney. This up-regulation of MHC class II proteins may stimulate the intragraft alloimmune response by promoting their recogn ... Full text Link to item Cite

What can knockout mice contribute to an understanding of hypertension?

Journal Article Curr Hypertens Rep · April 2000 The generation of knockout mice using homologous recombination in embryonic stem cells is a powerful tool for physiologic investigations. This experimental approach has provided unique insights into the study of hypertension. Studies using knockout mice ha ... Full text Link to item Cite

Failure of spermatogenesis in mouse lines deficient in the Na(+)-K(+)-2Cl(-) cotransporter.

Journal Article J Clin Invest · February 2000 The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) carries 1 molecule of Na(+) and K(+) along with 2 molecules of Cl(-) across the cell membrane. It is expressed in a broad spectrum of tissues and has been implicated in cell volume regulation and in ion transport ... Full text Link to item Cite

Regulation of sodium balance and blood pressure by the AT(1A) receptor for angiotensin II.

Journal Article Hypertension · February 2000 To examine the role of the angiotensin II (AT)(1A) receptor in the regulation of blood pressure and sodium balance, we measured systolic blood pressure responses in AT(1A) receptor-deficient (Agtr1a-/-) and wild-type (Agtr1a+/+) mice while dietary sodium c ... Full text Link to item Cite

Vasoconstrictor responses in thromboxane receptor knockout mice: tubuloglomerular feedback and ureteral obstruction.

Journal Article Acta Physiol Scand · January 2000 The role of thromboxane (TP) in the vasoconstriction induced by tubuloglomerular feedback or 18-h ureteral obstruction was studied in wild type mice (TP +/+), and in heterozygous (TP +/-) and homozygous TP receptor knockout mice (TPR -/-). TGF function was ... Full text Link to item Cite

Abnormal water metabolism in mice lacking the type 1A receptor for ANG II.

Journal Article Am J Physiol Renal Physiol · January 2000 Mice lacking AT(1A) receptors for ANG II have a defect in urinary concentration manifested by an inability to increase urinary osmolality to levels seen in controls after thirsting. This defect results in extreme serum hypertonicity during water deprivatio ... Full text Link to item Cite

Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway.

Journal Article J Clin Invest · December 1999 The renin-angiotensin system (RAS) is a key regulator of vascular tone and blood pressure. In addition, angiotensin II also has a number of cellular effects that may contribute to disease pathogenesis. Using Agtr1a(-/-) mice, which lack AT(1A) receptors fo ... Full text Link to item Cite

Renal vascular reactivity in mice: AngII-induced vasoconstriction in AT1A receptor null mice.

Journal Article J Am Soc Nephrol · December 1999 The present study describes methodology and its application to evaluate renal reactivity in acute studies on anesthetized mice. Renal blood flow (RBF) was measured using an ultrasonic transit-time flowmeter and a non-cannulating V-shaped probe. An intraren ... Full text Link to item Cite

Renal function in the at1A receptor knockout mouse during normal and volume-expanded conditions

Journal Article Kidney International · December 1, 1999 Background. Genetically altered mice lacking the AT1A angiotensin II (Ang II) receptor were used to examine the role of AT1A receptors in regulating renal hemodynamics, sodium excretion, glomerulotubular balance, and Ang II levels in plasma and kidney duri ... Cite

Renal function in the AT1A receptor knockout mouse during normal and volume-expanded conditions.

Journal Article Kidney Int · November 1999 BACKGROUND: Genetically altered mice lacking the AT1A angiotensin II (Ang II) receptor were used to examine the role of AT1A receptors in regulating renal hemodynamics, sodium excretion, glomerulotubular balance, and Ang II levels in plasma and kidney duri ... Full text Link to item Cite

Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice.

Journal Article Nat Med · October 1999 Platelet activation is characterized by shape change, induction of fibrinogen receptor expression and release of granular contents, leading to aggregation and plug formation. While this response is essential for hemostasis, it is also important in the path ... Full text Link to item Cite

Inducible nitric oxide synthase promotes cytokine expression in cardiac allografts but is not required for efficient rejection.

Journal Article J Heart Lung Transplant · September 1999 BACKGROUND: Inducible nitric oxide synthase (iNOS) is enhanced during acute rejection. Pharmacologic inhibition of nitric oxide synthase (NOS) activity has had variable effects on graft survival in a number of animal models. To further characterize the req ... Full text Link to item Cite

Identification of specific EP receptors responsible for the hemodynamic effects of PGE2.

Journal Article Am J Physiol · September 1999 To identify the E-prostanoid (EP) receptors that mediate the hemodynamic actions of PGE2, we studied acute vascular responses to infusions of PGE2 using lines of mice in which each of four EP receptors (EP1 through EP4) have been disrupted by gene targetin ... Full text Link to item Cite

Genetic manipulation of the renin-angiotensin system.

Journal Article Curr Opin Nephrol Hypertens · July 1999 Full text Link to item Cite

Gene targeting: applications in transplantation research.

Journal Article Kidney Int · July 1999 Gene targeting, the manipulation of gene in the mouse genome using homologous recombination in embryonic stem cells, is a powerful experimental tool that has been widely utilized in a number of disciplines. The ability to precisely alter genes in this way ... Full text Link to item Cite

Deficiency of 5-lipoxygenase abolishes sex-related survival differences in MRL-lpr/lpr mice.

Journal Article J Immunol · July 1, 1999 Leukotrienes, the 5-lipoxygenase (5LO) products of arachidonic acid metabolism, have many proinflammatory actions that have been implicated in the pathogenesis of a variety of inflammatory diseases. To investigate the role of LTs in autoimmune disease, we ... Link to item Cite

Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor.

Journal Article J Clin Invest · June 1999 Prostaglandins (PGs) are bioactive lipids that modulate a broad spectrum of biologic processes including reproduction and circulatory homeostasis. Although reproductive functions of mammals are influenced by PGs at numerous levels, including ovulation, fer ... Full text Link to item Cite

Chronic rejection of mouse kidney allografts.

Journal Article Kidney Int · May 1999 BACKGROUND: Chronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined. METHODS: To explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and exam ... Full text Link to item Cite

Fas on renal parenchymal cells does not promote autoimmune nephritis in MRL mice.

Journal Article Kidney Int · March 1999 BACKGROUND: Although Fas on pancreatic islets promotes autoimmune diabetes in mice, the role of Fas expression on kidney parenchymal cells during autoimmune disease is unknown. METHODS: To determine whether Fas on renal parenchymal cells promotes autoimmun ... Full text Link to item Cite

Effects of candesartan on angiotensin II-induced renal vasoconstriction in rats and mice.

Journal Article J Am Soc Nephrol · January 1999 This study determined the inhibitory effect of the angiotensin II (AngII) type I (AT1) receptor blocker candesartan on renal vascular reactivity in vivo. Reactivity to AngII before and during candesartan administration was assessed by measuring (by electro ... Link to item Cite

Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a receptor.

Journal Article Hypertension · January 1999 Angiotensin (Ang) type 1a (AT1a) receptors are critical in the control of blood pressure and water balance. Experiments were performed to determine the influence of dehydration on brain Ang receptors and plasma vasopressin (VP) in mice lacking this recepto ... Cite

Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a receptor.

Conference Hypertension · January 1999 Angiotensin (Ang) type 1a (AT1a) receptors are critical in the control of blood pressure and water balance. Experiments were performed to determine the influence of dehydration on brain Ang receptors and plasma vasopressin (VP) in mice lacking this recepto ... Full text Link to item Cite

Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II.

Journal Article Proc Natl Acad Sci U S A · December 22, 1998 The classically recognized functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separa ... Full text Link to item Cite

Urinary concentrating function in mice lacking EP3receptors for prostaglandin E2.

Journal Article Am J Physiol Renal Physiol · December 1, 1998 The actions of prostaglandin (PG) E2are mediated by four distinct classes of PGE2E-prostanoid (EP) receptors (EP1through EP4). However, the in vivo functions of the individual EP receptor subtypes have not been delineated. To study the functions of one of ... Full text Link to item Cite

Urinary concentrating function in mice lacking EP3 receptors for prostaglandin E2.

Journal Article The American journal of physiology · December 1998 The actions of prostaglandin (PG) E2 are mediated by four distinct classes of PGE2 E-prostanoid (EP) receptors (EP1 through EP4). However, the in vivo functions of the individual EP receptor subtypes have not been delineated. To study the functions of one ... Cite

Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.

Journal Article J Clin Invest · December 1, 1998 Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors. TP receptors have been implicated in the pathogenesis of cardiovascula ... Full text Link to item Cite

Inhibition of adenosine-1 receptor-mediated preglomerular vasoconstriction in AT1A receptor-deficient mice.

Journal Article Am J Physiol · December 1998 The effect of the adenosine type 1 receptor agonist N6-cyclohexyladenosine (CHA) on glomerular vascular reactivity was studied in male angiotensin II type 1A (AT1A) receptor knockout mice (9). Vascular reactivity was assessed as the response of stop-flow p ... Full text Link to item Cite

Immune cells in a mouse airway model of obliterative bronchiolitis.

Journal Article Am J Respir Cell Mol Biol · September 1998 Obliterative bronchiolitis (OB), a form of chronic lung rejection, affects 50% of all lung-transplant recipients and is a major cause of morbidity and mortality. We used the mouse tracheal allograft model of OB to quantitate inflammatory cells during disea ... Full text Link to item Cite

A genetic approach for studying the role of thromboxane A2 in the kidney.

Journal Article Kidney Int Suppl · September 1998 Thromboxane A2 (TxA2) has been implicated in a number of processes in normal kidney physiology and as a mechanism for injury in renal disease. TxA2 is a biologically active derivative of arachidonic acid and has potent vasoconstrictive and platelet-activat ... Full text Link to item Cite

Thromboxane A2modulates the fibrinolytic system in glomerular mesangial cells.

Journal Article Am J Physiol Renal Physiol · August 1, 1998 We examined the effects of thromboxane A2(TxA2) on the activities of the plasminogen-plasmin system in glomerular mesangial cells. When mesangial cells are exposed to the TxA2agonist U-46619, a substantial increase in production of plasminogen activator in ... Full text Link to item Cite

Gene targeting in physiological investigations: studies of the renin-angiotensin system.

Journal Article Am J Physiol Renal Physiol · June 1, 1998 Gene targeting using homologous recombination in embryonic stem cells provides an avenue for the direct application of precise molecular genetic interventions to the study of complex systems in whole animals. As such, it represents a powerful approach for ... Full text Link to item Cite

Downregulation of T cell receptor expression by CD8(+) lymphocytes in kidney allografts.

Journal Article J Clin Invest · June 1, 1998 Allospecific CD8(+) T lymphocytes are an important component of the cellular response in allograft rejection. These cells recognize and engage MHC class I antigens, leading to allospecific cytolytic responses and graft rejection. In mouse kidney allografts ... Full text Link to item Cite

Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice.

Journal Article Hypertension · May 1998 Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-ty ... Full text Link to item Cite

Pressure-overload hypertrophy is unabated in mice devoid of AT1A receptors.

Journal Article The American journal of physiology · March 1998 Mechanisms controlling cardiac growth are under intense investigation. Among these, the renin-angiotensin system has received great interest. In the current study, we tested the hypothesis that the renin-angiotensin system was not an obligate factor in car ... Cite

Pressure-overload hypertrophy is unabated in mice devoid of AT1A receptors.

Journal Article Am J Physiol · March 1998 Mechanisms controlling cardiac growth are under intense investigation. Among these, the renin-angiotensin system has received great interest. In the current study, we tested the hypothesis that the renin-angiotensin system was not an obligate factor in car ... Full text Link to item Cite

Renal growth and development in mice lacking AT1A receptors for angiotensin II.

Journal Article Am J Physiol · January 1998 To examine the role of the type 1A (AT1A) angiotensin receptor in renal growth and development, we analyzed F2 progeny from a series of crosses between F1 mice that were heterozygous for a targeted disruption of the AT1A receptor gene [Agtr1A-(+/-)]. Among ... Full text Link to item Cite

Inhibition of adenosine1 receptor-mediated glomerular vasoconstriction in AT1A-receptor deficient mice

Journal Article FASEB Journal · 1998 Previous studies have shown that tubuloglomerular feedback (TGF) responses are virtually abolished in angiotensin II 1A (AT1A) receptor null mutant mice (Ito et al., PNAS 1995). Since adenosine is a potential mediator of TGF-induced constriction we examine ... Cite

Effect of dehydration on angiotensin receptors in the AT-1a knockout mouse

Journal Article FASEB Journal · 1998 Changes in sodium/electrolyte status regulate angiotensin (Ang) receptor expression. Experiments were performed to determine the effect of dehydration on anterior pituitary (AP) and adrenal glomerulosa (AG) and medulla (AM) Ang receptors in AT-1aa knockout ... Cite

Functional separation of brain AT1A and AT1B receptors in AT1A knockout mice

Journal Article FASEB Journal · 1998 Angiotensin II (AII) type 1 receptors (AT1) are located in brain areas known to be involved in central AII-mediated cardiovascular and fluid balance regulation. Two genetically distinct subtypes of the AT1 receptor, AT1A and AT1B, have been identified and ... Cite

Angiotensin II causes renal vasoconstriction in mice with AT1A receptor deleted by gene targeting

Journal Article FASEB Journal · 1998 The aim of this study was to determine whether angiotensin II (Ang II) would affect renal blood flow in AT1A knockout mice. Acute renal hemodynamic studies were performed on 30-40 g mice with or without AT1A receptor during pentobarbital anesthesia. Blood ... Cite

Renal growth and development in mice lacking AT(1A) receptors for angiotensin II

Journal Article American Journal of Physiology - Renal Physiology · January 1, 1998 To examine the role of the type 1A (AT(1A)) angiotensin receptor in renal growth and development, we analyzed F2 progeny from a series of crosses between F1 mice that were heterozygous for a targeted disruption of the AT(1A) receptor gene [Agtr1A-(+/-)]. A ... Cite

Angiotensin II responses in at 1A receptor-deficient mice: A role for at 1B receptors in blood pressure regulation

Journal Article American Journal of Physiology · December 1, 1997 1997.-Most of the classic functions of the renin-angiotensin system are mediated by type 1 (AT 1) angiotensin receptors, of which two subtypes, AT 1A and AT 1B, have been identified. However, distinct functions for these two AT 1 receptors have been diffic ... Cite

Altered vasopressin axis in the AT-1a knockout mouse

Journal Article FASEB Journal · December 1, 1997 The AT1 receptor is involved in the regulation of vasopressin (VP) secretion. The effect of dehydration (2 days) on plasma and posterior pituitary (PP) VP was evaluated in the AT-1a knockout [KO(-/-)] and wild mice [KO(+/+)]. ChgBW P.Osm. P. VP PP VP Group ... Cite

The prostaglandin receptor EP4 triggers remodelling of the cardiovascular system at birth.

Journal Article Nature · November 6, 1997 Survival of newborn placental mammals depends on closure of the ductus arteriosus (DA), an arterial connection in the fetus which directs blood away from the pulmonary circulation and towards the placenta where oxygenation occurs. Here we show that morphol ... Full text Link to item Cite

Systemic autoimmune nephritogenic components induce CSF-1 and TNF-alpha in MRL kidneys.

Journal Article Kidney Int · October 1997 MRL-Faslpr mice are an appealing strain to understand the importance of cytokines in the pathogenesis of autoimmune renal destruction, since injury is rapid and predictable. Colony stimulating factor 1 (CSF-1) and tumor necrosis factor alpha (TNF-alpha) ar ... Full text Link to item Cite

The C-terminus of the thromboxane receptor contributes to coupling and desensitization in a mouse mesangial cell line.

Journal Article J Pharmacol Exp Ther · October 1997 To investigate regulatory domains of the thromboxane A2 (TxA2) receptor, we constructed a truncated form of the mouse TxA2 receptor and expressed it in a mesangial cell line. The mutant receptor lacked 22 amino acids in the C-terminus including four potent ... Link to item Cite

Modulation of eicosanoid metabolism in endothelial cells in a xenograft model. Role of cyclooxygenase-2.

Journal Article J Clin Invest · September 1, 1997 Lipid inflammatory mediators are thought to play a critical role in the pathogenesis of vascular injury. Among the events which might cause the synthesis of eicosanoids in blood vessels is activation of the complement. To evaluate how complement might infl ... Full text Link to item Cite

A genetic approach for studying the physiology of the type 1A (AT1A) angiotensin receptor.

Journal Article Semin Nephrol · September 1997 The ability to create targeted mutations in the mouse genome using homologous recombination in embryonic stem cells (gene targeting) has proved to be an extremely useful experimental approach. Recently, mouse lines have been produced with targeted disrupti ... Link to item Cite

Absence of tubuloglomerular feedback responses in AT1A receptor-deficient mice.

Journal Article Am J Physiol · August 1997 Experiments were performed in a recently generated strain of mice with an angiotensin II AT1A-receptor null mutation (M. Ito, M. I. Oliverio, P. J. Mannon, C. F. Best, N. Maeda, O. Smithies, and T. M. coffman. Proc. Natl. Acad. Sci. USA 92: 3521-3525, 1995 ... Full text Link to item Cite

Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.

Journal Article J Clin Invest · July 1, 1997 HIV-associated nephropathy (HIVAN) is a progressive glomerular and tubular disease that is increasingly common in AIDS patients and one of the leading causes of end stage renal disease in African Americans. A major unresolved issue in the pathogenesis of H ... Full text Link to item Cite

Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation.

Journal Article Am J Physiol · April 1997 Most of the classic functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors, of which two subtypes, AT1A and AT1B, have been identified. However, distinct functions for these two AT1 receptors have been difficult to sep ... Full text Link to item Cite

Angiotensin-II-receptors: new targets for antihypertensive therapy.

Journal Article Clin Cardiol · January 1997 The renin-angiotensin system regulates blood pressure and sodium homeostasis through a series of coordinated substrate-enzyme interactions. These interactions result in the production of angiotensin II (AII), which exerts a number of diverse biologic effec ... Full text Link to item Cite

Intravillous eicosanoid compartmentalization and regulation of placental blood flow.

Journal Article J Soc Gynecol Investig · 1997 OBJECTIVE: To determine the roles of the eicosanoids thromboxane and prostacyclin, and their compartmentalization, in the regulation of placental blood flow. METHODS: First, the sites of production of thromboxane and prostacyclin were determined within the ... Link to item Cite

Distribution of binding sites for thromboxane A2 in the mouse kidney.

Journal Article Am J Physiol · December 1996 Thromboxane A2 (TxA2) is a potent vasoconstrictor eicosanoid that has been implicated in the pathogenesis of both human and experimental renal diseases. The biological actions of TxA2 in the kidney are mediated through specific cell-surface receptors. In t ... Full text Link to item Cite

The intragraft CD8+ T cell response in renal allograft rejection in the mouse.

Journal Article Transplantation · July 15, 1996 To identify the role of donor class I alloantigens in regulating the CD8+ T cell response to a kidney allograft, we analyzed and compared the CD8+ infiltrate in kidney transplants from MHC class I-deficient (class I-) mouse donors and class I+ controls. On ... Full text Link to item Cite

Transplant approach establishes that kidneys are responsible for serum CSF-1 but require a stimulus in MRL-lpr mice.

Journal Article Kidney Int · January 1996 Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this st ... Full text Link to item Cite

Prevention of experimental cyclosporin-induced interstitial fibrosis by losartan and enalapril.

Journal Article The American journal of physiology · October 1995 The pathogenesis of renal scarring in chronic cyclosporin nephropathy is unknown. In this study, we evaluated the effects of renin-angiotensin system blockade by enalapril and losartan in a salt-dependent model of cyclosporin-associated chronic tubulointer ... Cite

Prevention of experimental cyclosporin-induced interstitial fibrosis by losartan and enalapril.

Journal Article Am J Physiol · October 1995 The pathogenesis of renal scarring in chronic cyclosporin nephropathy is unknown. In this study, we evaluated the effects of renin-angiotensin system blockade by enalapril and losartan in a salt-dependent model of cyclosporin-associated chronic tubulointer ... Full text Link to item Cite

Requirement of MIP-1 alpha for an inflammatory response to viral infection.

Journal Article Science · September 15, 1995 Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a chemokine that has pro-inflammatory and stem cell inhibitory activities in vitro. Its biologic role in vivo was examined in mice in which the gene encoding MIP-1 alpha had been disrupted. Homozygou ... Full text Link to item Cite

Effects of low-dose aspirin therapy on plasma levels of polyunsaturated fatty acids: a preliminary investigation.

Journal Article Am J Perinatol · September 1995 Polyunsaturated fatty acids play an important yet poorly understood role in pregnancy complications. We are interested in the effects of aspirin therapy on the metabolism of these compounds. To determine the effects of low-dose aspirin on plasma levels of ... Full text Link to item Cite

Late withdrawal of cyclosporine in stable renal transplant recipients.

Journal Article Am J Kidney Dis · September 1995 The use of cyclosporine (CsA) in renal transplantation has been associated with an improvement in 1-year graft survival, but has not changed the rate of late graft loss. We sought to determine whether the intent to withdraw CsA late after renal transplanta ... Full text Link to item Cite

Role of platelet activating factor in kidney transplant rejection in the rat.

Journal Article Kidney Int · August 1995 Platelet activating factor (PAF) is a potent lipid mediator with a broad range of biologic activities. Experimental evidence suggests that PAF plays a role in the pathogenesis of a variety of inflammatory processes including allograft rejection. In this st ... Full text Link to item Cite

In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium.

Journal Article Science · July 7, 1995 Many proteins are associated with the outer layer of the cell membrane through a posttranslationally added glycosyl phosphatidylinositol (GPI) anchor. The functional significance of this type of protein linkage is unclear, although it results in increased ... Full text Link to item Cite

Transport of phosphorothioate oligonucleotides in kidney: implications for molecular therapy.

Journal Article Kidney Int · May 1995 The systemic administration of phosphorothioated antisense oligonucleotides has been demonstrated to be an effective strategy for the control of gene expression. Because previous studies have suggested both hepatic and renal accumulation of systemically ad ... Full text Link to item Cite

Regulation of blood pressure by the type 1A angiotensin II receptor gene.

Journal Article Proc Natl Acad Sci U S A · April 11, 1995 The renin-angiotensin system plays a critical role in sodium and fluid homeostasis. Genetic or acquired alterations in the expression of components of this system are strongly implicated in the pathogenesis of hypertension. To specifically examine the phys ... Full text Link to item Cite

Genetic control of blood pressure and the angiotensinogen locus.

Journal Article Proc Natl Acad Sci U S A · March 28, 1995 Variants of the human angiotensinogen gene have been linked in some studies to increased circulating angiotensinogen levels and essential hypertension. To test for direct causality between genotypes at the angiotensinogen locus and blood pressures, we have ... Full text Link to item Cite

Rejection of kidney allografts by MHC class I-deficient mice.

Journal Article Transplantation · March 15, 1995 To evaluate the requirement for CD8+ T cells in kidney transplant rejection, we studied class I-deficient (class I-) mice that had received vascularized renal allografts. Because of the absence of MHC class I expression, these mice are grossly deficient in ... Full text Link to item Cite

Altered inflammatory responses in leukotriene-deficient mice.

Journal Article Proc Natl Acad Sci U S A · December 20, 1994 Leukotrienes have been implicated in the regulation of immune responses, including inflammation and immediate hypersensitivity reactions. Here, we describe the phenotypic analysis of leukotriene-deficient mice generated by inactivation of the 5-lipoxygenas ... Full text Link to item Cite

Fish oil feeding modulates leukotriene production in murine lupus nephritis.

Journal Article Prostaglandins · November 1994 Diets enriched with fish oil (FO) ameliorate kidney disease in the MRL-lpr/lpr murine model of lupus nephritis. Although the mechanisms of this effect are not known, FO is rich in the polyunsaturated fatty acid eicosapentaenoic acid (EPA) which may have pr ... Full text Link to item Cite

Modulation of thromboxane receptor activation in rat glomerular mesangial cells.

Journal Article Am J Physiol · September 1994 Rat glomerular mesangial cells were used to investigate mechanisms of thromboxane A2 (TxA2) receptor regulation in the kidney. Exposure of mesangial cells to the TxA2 agonist U-46619 for 10 min reduced subsequent TxA2-induced increases in inositol phosphat ... Full text Link to item Cite

Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.

Journal Article J Immunol · January 15, 1994 To investigate the role of leukotrienes in renal allograft rejection, we studied the effects of specific leukotriene inhibitors in a rat kidney transplant model. The enhanced renal production of leukotrienes observed in allograft recipients was reduced in ... Link to item Cite

Chronic thromboxane synthase inhibition with CGS 12970 in human cyclosporine nephrotoxicity.

Journal Article Transplantation · December 1993 CsA nephrotoxicity in rats is associated with an increase in renal thromboxane production. Treatment with selective thromboxane synthase inhibitors or receptor antagonists improves renal function in these animal models. In humans, it is unclear whether int ... Full text Link to item Cite

Alterations in renal interleukin-1 production during kidney transplant rejection in the rat. The effects of high-dose methylprednisolone.

Journal Article Transplantation · November 1993 To characterize the role of interleukin-1 in renal allograft rejection, we examined the temporal relationship of IL-1 production to changes in renal function and histology in a rat kidney transplantation model. In rat renal allografts, both glomerular filt ... Full text Link to item Cite

Effect of low-dose aspirin on thromboxane production and the antihypertensive effect of captopril.

Journal Article J Am Soc Nephrol · November 1993 Some of the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is through decreased kinin degradation, leading to enhanced production of vasodilator arachidonic acid ... Full text Link to item Cite

Improved renal function in mouse kidney allografts lacking MHC class I antigens.

Journal Article J Immunol · July 1, 1993 The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss o ... Link to item Cite

The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney.

Journal Article Transplantation · June 1993 The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney are examined. Kidneys were transplanted from Munich-Wistar (MW) rats to syngeneic controls and MHC-incompatible PVG strain recipients. We report on 4 group ... Full text Link to item Cite

Transgenic tubular cell expression of class II is insufficient to initiate immune renal injury.

Journal Article J Am Soc Nephrol · June 1993 Autoimmune disease in mouse models of lupus nephritis is associated with enhanced renal tubular epithelial cell (TEC) expression of major histocompatibility complex (MHC) class II (Ia) molecules. It is unknown whether de novo TEC expression of syngeneic la ... Full text Link to item Cite

The azaspirane SKF 105685 ameliorates renal allograft rejection in rats.

Journal Article J Am Soc Nephrol · April 1993 The azaspirane SKF 105685 (N,N-dimethyl-8, 8-dipropyl-2-azaspiro (4.5) decane-2-propanamine dihydrochloride) has been shown to attenuate or reverse the course of immunologic disease in several animal models, possibly through the induction of nonspecific su ... Full text Link to item Cite

Thromboxane binding and signal transduction in rat glomerular mesangial cells.

Journal Article Am J Physiol · February 1993 Thromboxane A2 (TxA2) stimulates contraction of glomerular mesangial cells. However, mesangial cell TxA2 receptors have not been previously characterized. We therefore investigated TxA2 binding and TxA2-associated signal transduction pathways in rat glomer ... Full text Link to item Cite

Characterization of glomerular thromboxane receptors in murine lupus nephritis.

Journal Article J Pharmacol Exp Ther · February 1993 Renal thromboxane (Tx) production is increased in the MRL-lpr murine model of lupus nephritis. To investigate the relationship between increased Tx production and number and affinity of Tx receptors, we measured binding of the Tx receptor antagonist [3H][S ... Link to item Cite

Immunologic mechanisms of transplant rejection.

Journal Article Curr Opin Nephrol Hypertens · December 1992 This article reviews recent progress in understanding the mechanisms of organ transplant rejection and focuses on studies that suggest new approaches to diagnosis and treatment. The alloimmune response is initiated by recognition of donor major histocompat ... Full text Link to item Cite

Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients.

Journal Article Clin Pharmacol Ther · December 1992 The effects of a 48-hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady-state plasma level of 1798 +/- 481 ng ... Full text Link to item Cite

Thromboxane augmentation of alloreactive T cell function.

Journal Article Transplantation · September 1992 Thromboxane (Tx) plays a vital role in the dysfunction and ultimate rejection of MHC-disparate renal allografts. In addition to its potent vasoconstrictory properties, in vivo studies have implied that Tx is capable of promoting immune cytotoxic T cell fun ... Full text Link to item Cite

Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr mice.

Journal Article Clin Immunol Immunopathol · August 1992 MRL-lpr/lpr mice develop an inflammatory arthritis in association with other manifestations of autoimmunity. Although a variety of immune cell disturbances have been described in these mice, the relationship of these abnormalities to the pathogenesis of ar ... Full text Link to item Cite

Crosstransplantation of kidneys in normal and Hyp mice. Evidence that the Hyp mouse phenotype is unrelated to an intrinsic renal defect.

Journal Article J Clin Invest · May 1992 Although deranged phosphate transport is the fundamental abnormality in X-linked hypophosphatemic (XLH) rickets, it remains unknown if this defect is the consequence of an intrinsic kidney abnormality or aberrant production of a humoral factor. To discrimi ... Full text Link to item Cite

Thromboxane receptor blockade reduces renal injury in murine lupus nephritis.

Journal Article Kidney Int · April 1992 To investigate the role of thromboxane A2 (TxA2) in murine lupus, we assessed the effects of the specific thromboxane receptor antagonist GR32191 on immune complex glomerulonephritis in MRL-lpr/lpr mice. Forty mg/kg/day GR32191 was given by twice daily sub ... Full text Link to item Cite

Effects of thromboxane synthase inhibition with CGS 13080 in human cyclosporine nephrotoxicity.

Journal Article Kidney Int · January 1992 Cyclosporine is a potent immunosuppressive agent, however, its use is limited by nephrotoxicity. Increased production of the potent vasoconstrictor thromboxane A2 contributes to cyclosporine nephrotoxicity in animal models, but the role of thromboxane in h ... Full text Link to item Cite

Physiologic role for enhanced renal thromboxane production in murine lupus nephritis.

Journal Article Prostaglandins · July 1991 To investigate the physiologic significance of enhanced renal thromboxane production in murine lupus nephritis, we measured renal hemodynamics and eicosanoid production in MRL-lpr/lpr mice from 8 to 20 weeks of age. Over this age range, MRL-lpr/lpr mice de ... Full text Link to item Cite

Enhanced renal leukotriene production in murine lupus: role of lipoxygenase metabolites.

Journal Article Kidney Int · January 1991 To investigate the potential role of leukotrienes in murine lupus, we measured renal hemodynamics and renal leukotriene production in MRL-lpr/lpr mice at 12 and 20 weeks of age. Over this age range, these animals develop overt manifestations of autoimmune ... Full text Link to item Cite

Atrial natriuretic peptide-induced changes in renal prostacyclin production in ureteral obstruction.

Journal Article Am J Physiol · February 1990 Ureteral obstruction is characterized by a marked reduction in renal hemodynamic function that is mediated in part by increased production of the vasoconstrictor eicosanoid thromboxane. However, animals with bilateral ureteral obstruction (BUO) sustain les ... Full text Link to item Cite

Thromboxane receptor blockade improves cyclosporine nephrotoxicity in rats.

Journal Article Prostaglandins · February 1990 Cyclosporine A (CyA) nephrotoxicity is associated with impaired renal hemodynamic function and increased production of the vasoconstrictor eicosanoid thromboxane A2 (TxA2). In CyA toxic rats, renal dysfunction can be partially reversed by inhibitors of thr ... Full text Link to item Cite

High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes.

Journal Article J Lab Clin Med · November 1989 In diabetic rats glomerular morphologic damage is exacerbated by feeding a protein-rich diet. Protein feeding alters arachidonic acid metabolism in other models of renal disease, and there is evidence that the arachidonic acid metabolite thromboxane plays ... Link to item Cite

Association of chronic thromboxane inhibition with reduced in situ cytotoxic T cell activity in rejecting rat renal allografts.

Journal Article Transplantation · October 1989 The development of allospecific cellular immunity during acute rat renal allograft rejection parallels alterations occurring in arachidonic acid metabolism, including increased production of the vasoconstrictor eicosanoid thromboxane A2 (TxA2). We have pre ... Link to item Cite

Post-transplant hypertension in the rat: effects of captopril and native nephrectomy.

Journal Article Kidney Int · July 1989 In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the conf ... Full text Link to item Cite

Chronic thromboxane inhibition preserves function of rejecting rat renal allografts.

Journal Article Kidney Int · January 1989 Increased production of thromboxane (TX) by rejecting renal allografts results in significant and partially reversible renal vasoconstriction. In this study, we evaluated the potential benefit of chronically administering the TX synthetase inhibitor OKY-04 ... Full text Link to item Cite

Effect of dietary fish oil supplementation on eicosanoid production by rat renal allografts.

Journal Article Transplantation · February 1988 Acute renal allograft rejection is associated with significant alterations in renal arachidonic acid (AA) metabolism including increased production of the vasoconstrictor eicosanoid thromboxane (TX)A2. TX synthetase inhibition improves function of rejectin ... Full text Link to item Cite

Evidence that pretransplant donor blood transfusion prevents rat renal allograft dysfunction but not the in situ cellular alloimmune or morphologic manifestations of rejection.

Journal Article Transplantation · January 1988 The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder str ... Full text Link to item Cite

Comparison of intravenous digital subtraction angiography and conventional arteriography in defining renal anatomy.

Journal Article Transplantation · January 1988 Intravenous digital subtraction renal angiography (IV-DSRA) is frequently used in the preoperative evaluation of living-related (LR) kidney donors. However, the true accuracy of IV-DSRA in the donor population is difficult to assess since abnormalities of ... Full text Link to item Cite

Associations between rat renal allograft function, inflammation, and host immunity

Journal Article Transplantation Proceedings · April 27, 1987 Cite

Evidence that renal prostaglandin and thromboxane production is stimulated in chronic cyclosporine nephrotoxicity.

Journal Article Transplantation · February 1987 Previous reports suggest that cyclosporine (CsA) may have direct effects on arachidonic acid (AA) metabolism in several different tissues. However, the effects of CsA on renal eicosanoid production are unclear. Furthermore, the potential role of changes in ... Full text Link to item Cite

Bilateral native nephrectomy improves renal isograft function in rats.

Journal Article Kidney Int · July 1986 Bilateral native nephrectomy has been suggested to improve renal allograft survival in man. This effect may be most prominent in patients experiencing acute tubular necrosis following transplantation. Thus, native kidneys may alter the course of ischemic a ... Full text Link to item Cite

Thromboxane synthetase inhibition improves function of hydronephrotic rat kidneys.

Journal Article Am J Physiol · February 1986 Twenty-four hours of complete unilateral ureteral obstruction (UUO) produces intense renal vasconstriction in the rat even after release of obstruction. In the ex vivo perfused hydronephrotic rabbit kidney, bradykinin stimulates increased production of the ... Full text Link to item Cite

Lipid mediators in acute renal allograft rejection

Journal Article Transplantation Proceedings · January 1, 1986 Cite

Functional role of thromboxane production by acutely rejecting renal allografts in rats.

Journal Article J Clin Invest · April 1985 We investigated the role of thromboxane in mediating the reduction in renal function and renal blood flow characteristic of acute renal allograft rejection. We transplanted kidneys from Lewis rats to Brown-Norway recipients. By the third day after transpla ... Full text Link to item Cite

Effects of two models of hypercalcemia on renal acid base metabolism.

Journal Article Kidney Int · April 1982 The effects of two models of chronic hypercalcemia on renal acid-base metabolism were studied in rats. In the first series of experiments, rats were rendered hyperparathyroid by the autologous grafting of 20 to 24 parathyroid glands into a single recipient ... Full text Link to item Cite

Effects of two nonsteroidal anti-inflammatory drugs, indomethacin and oxaprozin, on the kidney.

Journal Article Clin Pharmacol Ther · November 1980 Nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to cause sodium retention and to decrease glomerular filtration rate (GFR). We studied the effects of two such drugs, indomethacin and oxaprozin, a new propionic acid derivative, on renal functi ... Full text Link to item Cite