Scholars@Duke
Timothy Joseph McMahon

Timothy Joseph McMahon

Professor of Medicine
Medicine, Pulmonary, Allergy, and Critical Care Medicine
tim.mcmahon@duke.edu
DUMC 2650, 203 Research Drive, Durham, NC 27710
MSRB1, Rm 275, DUMC 2650, 203 Research Drive, Durham, NC 27710

Selected Publications

The high price of equity in pulse oximetry: A cost evaluation and need for interim solutions.

Journal Article PLOS Digit Health · September 2024 Disparities in pulse oximetry accuracy, disproportionately affecting patients of color, have been associated with serious clinical outcomes. Although many have called for pulse oximetry hardware replacement, the cost associated with this replacement is not ... Full text Link to item Cite

Endothelial LAT1 (SLC7A5) Mediates S-Nitrosothiol Import and Modulates Respiratory Sequelae of Red Blood Cell Transfusion In Vivo.

Journal Article Thromb Haemost · July 2024 BACKGROUND:  Increased adhesivity of red blood cells (RBCs) to endothelial cells (ECs) may contribute to organ dysfunction in malaria, sickle cell disease, and diabetes. RBCs normally export nitric oxide (NO)-derived vascular signals, facilitating blood fl ... Full text Open Access Link to item Cite

Toward Translational Impact of Low-Glucose Strategies on Red Blood Cell Storage Optimization.

Journal Article ACS Pharmacol Transl Sci · March 8, 2024 Transfusion of stored red blood cells (RBCs) to patients is a critical component of human healthcare. Following purification from whole blood, RBCs are stored in one of many media known as additive solutions for up to 42 days. However, during the storage p ... Full text Link to item Cite

Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.

Journal Article Front Physiol · 2024 Efficient distribution of oxygen (O2) to the tissues in mammals depends on the evolved ability of red blood cell (RBC) hemoglobin (Hb) to sense not only O2 levels, but metabolic cues such as pH, PCO2, and organic phosphates, and then dispense or take up ox ... Full text Link to item Cite

Novel Normoglycemic Human RBC Storage: Post-transfusion Respiratory Sequelae in Nude Mice

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2023 Cite

Multiomic, Mass Spectrometry-based Analysis of Dried Blood: Toward Deep Phenotyping of Sepsis

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · 2023 Cite

Design, Synthesis, and Investigation of Novel Nitric Oxide (NO)-Releasing Aromatic Aldehydes as Drug Candidates for the Treatment of Sickle Cell Disease.

Journal Article Molecules · October 12, 2022 Sickle cell disease (SCD) is caused by a single-point mutation, and the ensuing deoxygenation-induced polymerization of sickle hemoglobin (HbS), and reduction in bioavailability of vascular nitric oxide (NO), contribute to the pathogenesis of the disease. ... Full text Link to item Cite

A 3D-printed transfusion platform reveals beneficial effects of normoglycemic erythrocyte storage solutions and a novel rejuvenating solution.

Journal Article Lab Chip · March 29, 2022 A set of 3D-printed analytical devices were developed to investigate erythrocytes (ERYs) processed in conventional and modified storage solutions used in transfusion medicine. During storage, prior to transfusion into a patient recipient, ERYs undergo many ... Full text Open Access Link to item Cite

Severe Acute Respiratory Syndrome Coronavirus 2 Convalescent Plasma Versus Standard Plasma in Coronavirus Disease 2019 Infected Hospitalized Patients in New York: A Double-Blind Randomized Trial.

Journal Article Crit Care Med · July 1, 2021 OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determi ... Full text Link to item Cite

Pannexin 1 channels control the hemodynamic response to hypoxia by regulating O2-sensitive extracellular ATP in blood.

Journal Article Am J Physiol Heart Circ Physiol · March 1, 2021 Pannexin 1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contribute to hypoxic vasodilation, a mechanism that ... Full text Open Access Link to item Cite

Generation and Export of Red Blood Cell ATP in Health and Disease.

Journal Article Front Physiol · 2021 Metabolic homeostasis in animals depends critically on evolved mechanisms by which red blood cell (RBC) hemoglobin (Hb) senses oxygen (O2) need and responds accordingly. The entwined regulation of ATP production and antioxidant systems within the RBC also ... Full text Link to item Cite

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies.

Journal Article Respir Res · November 19, 2020 BACKGROUND: Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-re ... Full text Open Access Link to item Cite

HGT in the human and skin commensal Malassezia: A bacterially derived flavohemoglobin is required for NO resistance and host interaction.

Journal Article Proc Natl Acad Sci U S A · July 7, 2020 The skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions. Malassezia are the most abundant fungal skin inhabitant of warm-blooded animals and hav ... Full text Open Access Link to item Cite

Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease.

Journal Article Blood Transfus · May 2020 BACKGROUND: Red blood cell (RBC) exchange (RCE) transfusion therapy is indicated for certain patients with sickle cell disease (SCD). Although beneficial, this therapy is costly and inconvenient to patients, who may require it monthly or more often. Identi ... Full text Link to item Cite

Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.

Journal Article Blood Adv · September 10, 2019 Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All t ... Full text Open Access Link to item Cite

Transfusion of Red Blood Cells in Mice with Endothelial Deletion of the S-Nitrosothiol Transporter LAT1

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2019 Link to item Cite

Decreased ATP Export from Erythrocytes in Murine Sepsis

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2019 Link to item Cite

Red Blood Cell Deformability, Vasoactive Mediators, and Adhesion.

Journal Article Front Physiol · 2019 Healthy red blood cells (RBCs) deform readily in response to shear stress in the circulation, facilitating their efficient passage through capillaries. RBCs also export vasoactive mediators in response to deformation and other physiological and pathologica ... Full text Open Access Link to item Cite

Drebrin regulates angiotensin II-induced aortic remodelling.

Journal Article Cardiovasc Res · November 1, 2018 AIMS: The actin-binding protein Drebrin is up-regulated in response to arterial injury and reduces smooth muscle cell (SMC) migration and proliferation through its interaction with the actin cytoskeleton. We, therefore, tested the hypothesis that SMC Drebr ... Full text Open Access Link to item Cite

Proceedings of the Food and Drug Administration's public workshop on new red blood cell product regulatory science 2016.

Journal Article Transfusion · January 2018 The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop wa ... Full text Link to item Cite

CD163 Protects Against Ozone Increased Susceptibility to Bacterial Pneumonia

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2018 Link to item Cite

Red blood cell phenotype fidelity following glycerol cryopreservation optimized for research purposes.

Journal Article PLoS One · 2018 Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter and sample analysis, we developed a research-specific RBC cryopreservation protocol and assessed its impact on da ... Full text Open Access Link to item Cite

Biomarkers in Pulmonary Vascular Disease: Gauging Response to Therapy.

Journal Article Am J Cardiol · October 15, 2017 Biomarkers are increasingly being investigated in the treatment of pulmonary vascular disease. In particular, the signaling pathways targeted by therapies for pulmonary arterial hypertension provide biomarkers that potentially can be used to guide therapy ... Full text Link to item Cite

Antagonists of the system L neutral amino acid transporter (LAT) promote endothelial adhesivity of human red blood cells.

Journal Article Thromb Haemost · June 28, 2017 The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobi ... Full text Open Access Link to item Cite

Red Blood Cell Hemoglobin-Bound Nitric Oxide In Human Blood Stored For Acute Normovolemic Hemodilution (anh)

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2017 Link to item Cite

The Role Of L-Amino Acid Transporter (lat-1) In The Hypoxia-Induced Export Of Anti-Adhesive S-Nitrosothiols (snos)

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2017 Link to item Cite

S-Nitrosylated fetal hemoglobin in neonatal human blood.

Journal Article Biochem Biophys Res Commun · May 13, 2016 BACKGROUND: Nitric oxide (NO) and its derivatives play important roles in the cardiopulmonary transition upon birth and in other oxygen-sensitive developmental milestones. One mechanism for the coupling of oxygen sensing and signaling by NO species is via ... Full text Link to item Cite

Toward Theranostic Biomarkers In Pulmonary Hypertension

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2016 Link to item Cite

Platelets promote pulmonary pull of polys.

Journal Article Blood · November 5, 2015 In this issue of Blood, Guo and colleagues report the intriguing discovery of a unique proinflammatory role for platelet-derived Dickkopf-1 (Dkk1), a secreted antagonist of pulmonary epithelial repair programs that use the canonical Wnt/β-catenin pathway, ... Full text Link to item Cite

Renitrosylation of banked human red blood cells improves deformability and reduces adhesivity.

Journal Article Transfusion · October 2015 Featured Publication BACKGROUND: Transfusion of red blood cells (RBCs) is a frequent health care practice. However, unfavorable consequences may occur from transfusions of stored RBCs and are associated with RBC changes during storage. Loss of S-nitrosohemoglobin (SNO-Hb) and ... Full text Link to item Cite

Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion.

Journal Article Am J Physiol Heart Circ Physiol · December 15, 2014 Featured Publication Transfusion of banked red blood cells (RBCs) has been associated with poor cardiovascular outcomes. Storage-induced alterations in RBC glycolytic flux, attenuated ATP export, and microvascular adhesion of transfused RBCs in vivo could contribute, but the u ... Full text Link to item Cite

Randomized study of washing 40- to 42-day-stored red blood cells.

Journal Article Transfusion · October 2014 BACKGROUND: Pretransfusion washing of red blood cells (RBCs) stored for a longer duration may have theoretical advantages but few data exist to support this practice. In many hospital settings, use of a point-of-care cell washer could conceivably be used t ... Full text Link to item Cite

Proteomic analysis of the NOS2 interactome in human airway epithelial cells.

Journal Article Nitric Oxide · November 1, 2013 The cytokine-inducible isoform of nitric oxide synthase (NOS2) is constitutively expressed in human respiratory epithelia and is upregulated in inflammatory lung disease. Here, we sought to better define the protein interactions that may be important for N ... Full text Link to item Cite

Parallel assay of oxygen equilibria of hemoglobin.

Journal Article Anal Biochem · October 1, 2013 Methods to systematically analyze in parallel the function of multiple protein or cell samples in vivo or ex vivo (i.e., functional proteomics) in a controlled gaseous environment have so far been limited. Here, we describe an apparatus and procedure that ... Full text Link to item Cite

Automated measurement of blood flow velocity and direction and hemoglobin oxygen saturation in the rat lung using intravital microscopy.

Journal Article Am J Physiol Lung Cell Mol Physiol · January 15, 2013 Intravital microscopy of the pulmonary microcirculation in research animals is of great scientific interest for its utility in identifying regional changes in pulmonary microcirculatory blood flow. Although feasibility studies have been reported, the pulmo ... Full text Link to item Cite

The clinical role of soluble guanylyl cyclase stimulators

Journal Article Current Topics in Pharmacology · January 1, 2013 Soluble guanylyl cyclase (sGC) catalyzes cyclic guanosine 3 ' ,5 ' -monophosphate (cGMP) synthesis. cGMP is involved in relaxation of vascular smooth muscle, modulation of inflammation, inhibition of platelet aggregation, and control of vascular permeabili ... Cite

Impact of transfusion of autologous 7- versus 42-day-old AS-3 red blood cells on tissue oxygenation and the microcirculation in healthy volunteers.

Journal Article Transfusion · November 2012 BACKGROUND: Stored red blood cells (RBCs) accumulate biochemical and biophysical changes. Maximum storage duration is based on acceptable in vitro characteristics and 24-hour survival, but not RBC function. Relatively little is known about the impact of RB ... Full text Link to item Cite

Transpulmonary flux of S-nitrosothiols and pulmonary vasodilation during nitric oxide inhalation: role of transport.

Journal Article Am J Respir Cell Mol Biol · July 2012 Featured Publication Inhaled nitric oxide (iNO) is used to treat pulmonary hypertension and is being investigated for prevention of bronchopulmonary dysplasia in neonates. Extrapulmonary effects of iNO are widely recognized, but the underlying chemistry and pharmacology are po ... Full text Link to item Cite

The opprobrium of Big Tobacco.

Journal Article Am J Respir Crit Care Med · May 1, 2012 Full text Link to item Cite

Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

Journal Article J Pediatr · February 2012 OBJECTIVE: To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. STUDY DESIGN: In this single center study, 5 sequential blood samples were collecte ... Full text Link to item Cite

Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion.

Journal Article Crit Care Med · November 2011 Featured Publication OBJECTIVE: Transfusion of red blood cells has been linked to disappointing clinical outcomes in the critically ill, but specific mechanisms of organ dysfunction after transfusion remain poorly understood. We tested the hypothesis that red blood cell storag ... Full text Link to item Cite

Red Blood Cell Release Of ATP Prevents Endothelial Adhesion: Implications For Post-Transfusion Lung Dysfunction

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2011 Link to item Cite

Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.

Journal Article Free Radic Biol Med · July 15, 2010 The pathway by which inhaled NO gas enters pulmonary alveolar epithelial cells has not been directly tested. Although the expected mechanism is diffusion, another route is the formation of S-nitroso-L-cysteine, which then enters the cell through the L-type ... Full text Link to item Cite

Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter.

Journal Article Am J Physiol Lung Cell Mol Physiol · July 2008 Nitric oxide (NO) effects are often mediated via S-nitrosothiol (SNO) formation; SNO uptake has recently been shown to be mediated in some cell types via system L-type amino acid transporters (LAT-1, 2). Inhaled NO therapy may exert some biological effects ... Full text Link to item Cite

Evolution of adverse changes in stored RBCs.

Journal Article Proc Natl Acad Sci U S A · October 23, 2007 Featured Publication Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit ... Full text Link to item Cite

Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery.

Journal Article Physiology (Bethesda) · April 2007 Featured Publication The biology of NO (nitric oxide) is poorly explained by the activity of the free radical NO ((.)NO) itself. Although (.)NO acts in an autocrine and paracrine manner, it is also in chemical equilibrium with other NO species that constitute stable stores of ... Full text Link to item Cite

Excitation-contraction coupling in airway smooth muscle.

Journal Article J Biol Chem · October 6, 2006 Featured Publication Excitation-contraction (EC) coupling in striated muscles is mediated by the cardiac or skeletal muscle isoform of voltage-dependent L-type Ca(2+) channel (Ca(v)1.2 and Ca(v)1.1, respectively) that senses a depolarization of the cell membrane, and in respon ... Full text Link to item Cite

Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin.

Journal Article Proc Am Thorac Soc · April 2006 Featured Publication Early applications of inhaled nitric oxide (iNO), typically in the treatment of diseases marked by acute pulmonary hypertension, were met by great enthusiasm regarding the purported specificity of iNO: vasodilation by iNO was specific to the lung (without ... Full text Link to item Cite

Physician subsidies for tobacco advertising.

Journal Article Am J Respir Crit Care Med · January 15, 2006 Full text Link to item Cite

S-nitrosoglutathione inhibits alpha1-adrenergic receptor-mediated vasoconstriction and ligand binding in pulmonary artery.

Journal Article Am J Physiol Lung Cell Mol Physiol · January 2006 Endogenous nitric oxide donor compounds (S-nitrosothiols) contribute to low vascular tone by both cGMP-dependent and -independent pathways. We have reported that S-nitrosoglutathione (GSNO) inhibits 5-hydroxytryptamine (5-HT)-mediated pulmonary vasoconstri ... Full text Link to item Cite

Redox activation of intracellular calcium release channels (ryanodine receptors) in the sustained phase of hypoxia-induced pulmonary vasoconstriction.

Journal Article Chest · December 2005 Hypoxia-induced pulmonary vasoconstriction (HPV) is an important adaptive process that remains incompletely understood. In preconstricted rat pulmonary arteries (inner diameter, 250 to 400 microm), hypoxia (pO2 approximately 10 mm Hg) induces an initial tr ... Full text Link to item Cite

A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension.

Journal Article Proc Natl Acad Sci U S A · October 11, 2005 Featured Publication The mechanism by which hypoxia [low partial pressure of O(2) (pO(2))] elicits signaling to regulate pulmonary arterial pressure is incompletely understood. We considered the possibility that, in addition to its effects on smooth muscle, hypoxia may influen ... Full text Link to item Cite

A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension.

Journal Article Pediatr Res · September 2005 Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extra ... Full text Link to item Cite

Oxygen regulation of tumor perfusion by S-nitrosohemoglobin reveals a pressor activity of nitric oxide.

Journal Article Circ Res · May 27, 2005 In erythrocytes, S-nitrosohemoglobin (SNO-Hb) arises from S-nitrosylation of oxygenated hemoglobin (Hb). It has been shown that SNO-Hb behaves as a nitric oxide (NO) donor at low oxygen tensions. This property, in combination with oxygen transport capacity ... Full text Link to item Cite

Hemoglobin conformation couples erythrocyte S-nitrosothiol content to O2 gradients.

Journal Article Proc Natl Acad Sci U S A · April 19, 2005 It is proposed that the bond between nitric oxide (NO) and the Hb thiol Cys-beta(93) (SNOHb) is favored when hemoglobin (Hb) is in the relaxed (R, oxygenated) conformation, and that deoxygenation to tense (T) state destabilizes the SNOHb bond, allowing tra ... Full text Link to item Cite

Red Blood Cell S-Nitrosohemoglobin Deficiency in Pulmonary Arterial Hypertension.

Conference Blood · November 16, 2004 AbstractRecent studies have suggested that binding of oxygen to hemoglobin (Hb) facilitates reactions of nitric oxide (NO) that lead to production of S-nitrosohemoglobin (SNO-Hb), and that vasodilator S-nitr ... Full text Cite

Hypoxic Vasodilation by Red Blood Cells and Impairment in Vascular Disorders.

Conference Blood · November 16, 2004 AbstractPhysiological O2 gradients are principal regulators of blood flow in the microcirculation: position-to-position changes in hemoglobin (Hb) O2 saturation are coupled to regulated vasodilation (“hypoxi ... Full text Cite

Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock

Conference NITRIC OXIDE-BIOLOGY AND CHEMISTRY · August 1, 2004 Link to item Cite

Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock.

Journal Article Cell · February 20, 2004 The current perspective of NO biology is formulated predominantly from studies of NO synthesis. The role of S-nitrosothiol (SNO) formation and turnover in governing NO-related bioactivity remains uncertain. We generated mice with a targeted gene deletion o ... Full text Link to item Cite

Hemoglobin and nitric oxide.

Journal Article N Engl J Med · July 24, 2003 Link to item Cite

Hemoglobin and nitric oxide.

Journal Article N Engl J Med · July 24, 2003 Featured Publication Full text Link to item Cite

Hemoglobin and nitric oxide

Journal Article NEW ENGLAND JOURNAL OF MEDICINE · July 24, 2003 Link to item Cite

S-nitrosylation in health and disease.

Journal Article Trends Mol Med · April 2003 Featured Publication S-nitrosylation is a ubiquitous redox-related modification of cysteine thiol by nitric oxide (NO), which transduces NO bioactivity. Accumulating evidence suggests that the products of S-nitrosylation, S-nitrosothiols (SNOs), play key roles in human health ... Full text Link to item Cite

Nitric oxide in the human respiratory cycle.

Journal Article Nat Med · July 2002 Featured Publication Interactions of nitric oxide (NO) with hemoglobin (Hb) could regulate the uptake and delivery of oxygen (O(2)) by subserving the classical physiological responses of hypoxic vasodilation and hyperoxic vasconstriction in the human respiratory cycle. Here we ... Full text Link to item Cite

Pulmonary vasoconstriction by serotonin is inhibited by S-nitrosoglutathione.

Journal Article Am J Physiol Lung Cell Mol Physiol · May 2002 Nitric oxide (NO) functions as an endothelium-derived relaxing factor by activating guanylate cyclase to increase cGMP levels. However, NO and related species may also regulate vascular tone by cGMP-independent mechanisms. We hypothesized that naturally oc ... Full text Link to item Cite

S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.

Journal Article Proc Natl Acad Sci U S A · May 8, 2001 NO synthases are widely distributed in the lung and are extensively involved in the control of airway and vascular homeostasis. It is recognized, however, that the O(2)-rich environment of the lung may predispose NO toward toxicity. These Janus faces of NO ... Full text Link to item Cite

Nitric oxide in the respiratory cycle in human health and disease

Journal Article FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2001 Link to item Cite

Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin.

Journal Article J Biol Chem · June 2, 2000 Featured Publication S-Nitrosohemoglobin (SNO-Hb) is a vasodilator whose activity is allosterically modulated by oxygen ("thermodyamic linkage"). Blood vessel contractions are favored in the oxygenated structure, and vasorelaxant activity is "linked" to deoxygenation, as illus ... Full text Link to item Cite

S-nitrosylation of hemoglobin increases its oxygen affinity

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · March 1, 1999 Link to item Cite

Concerted nitric oxide/oxygen delivery by hemoglobin.

Journal Article Methods Enzymol · 1999 Featured Publication Full text Link to item Cite

Thermodynamic linkage relationships in S-nitrosohemoglobin: Oxygen binding and vasoactivity

Journal Article FREE RADICAL BIOLOGY AND MEDICINE · January 1, 1999 Link to item Cite

In vivo gene transfer of nitric oxide synthase enhances vasomotor function in carotid arteries from normal and cholesterol-Fed rabbits.

Journal Article Circulation · November 3, 1998 BACKGROUND: The vascular endothelium is anatomically intact but functionally abnormal in preatherosclerotic states, and an early deficit in the bioavailability of nitric oxide (NO) or related molecules has been described in both humans and animal models. W ... Full text Link to item Cite

The effect of hyperbaric oxygen on pulmonary vascular tone.

Journal Article ANESTHESIOLOGY · September 1, 1998 Link to item Cite

Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure.

Journal Article Lancet · May 2, 1998 BACKGROUND: Nitric oxide (NO) gas concentrations are high in the expired air of individuals with asthma, but not consistently so in the expired air of people with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the concentrations of whi ... Full text Link to item Cite

Nitric oxide synthase gene transfer corrects deficient endothelial vasmotor function in hypercholesterolaemic rabbits

Journal Article Heart · May 1, 1998 Background: The vascular endothelium is anatomically intact but functionally abnormal in preatherosclerotic states. In particular, nitric oxide (NO) bioavailability is reduced and may play a role in disease progression. We investigated whether targeted vas ... Cite

Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient.

Journal Article Science · June 27, 1997 The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric oxide (NO) to cysteinebeta93, forming S-nitrosohemoglobin. Deoxygenation is accompanied by an allosteric transition in S-nitrosohemoglobin [from the R (oxygenated) to the T (d ... Full text Link to item Cite

In vivo adenoviral gene transfer of nitric oxide synthase augments or restores vascular no production

Journal Article Heart · May 1, 1997 Nitric oxide (NO) has key regulatory roles in the cardiovascular system. NO production is defective in injured or diseased vessels and restoration of NO production inhibits the sequelae of vessel injury. The nitric oxide synthase (NOS) isoforms are therefo ... Cite

Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation.

Journal Article Am J Physiol · December 1996 The effects of the vascular selective nonsulfonylurea guanidine ATP-sensitive K+ (KATP+) channel-blocking agent U-37883A on vasodilator and vasoconstrictor responses were investigated in the pulmonary and hindlimb vascular beds of the cat. Under elevated t ... Full text Link to item Cite

Role of K+ATP channels and EDRF in reactive hyperemia in the hindquarters vascular bed of cats.

Journal Article Am J Physiol · November 1995 The mechanism underlying reactive hyperemia was investigated in the feline hindquarters vascular bed under natural- and constant-flow conditions. A 30-s occlusion of the distal aorta produced a marked hyperemic increase in distal aortic blood flow that was ... Full text Link to item Cite

Comparative effects of L-NNA and alkyl esters of L-NNA on pulmonary vasodilator responses to ACh, BK, and SP.

Journal Article Am J Physiol · June 1994 The comparative effects of the nitric oxide (NO) synthase inhibitors N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME), and N omega-nitro-L-arginine benzyl ester (L-NABE) on baseline tone and on vasodilator responses to acety ... Full text Link to item Cite

Comparison of pressor responses to angiotensin I, II, and III in pulmonary vascular bed of cats.

Journal Article Am J Physiol · June 1994 Pulmonary vascular responses to angiotensin (ANG) peptides were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Intralobar injections of ANG I, II, and III caused dose-related increases in l ... Full text Link to item Cite

Analysis of responses to bradykinin in the pulmonary vascular bed of the cat.

Journal Article Am J Physiol · June 1994 Responses to bradykinin (BK) were investigated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was elevated to a high steady level. Under elevated-t ... Full text Link to item Cite

Comparison of responses to pituitary adenylate cyclase activating peptides 38 and 27 in the pulmonary vascular bed of the cat.

Journal Article Eur J Pharmacol · October 12, 1993 Responses to pituitary adenylate cyclase activating polypeptide (PACAP)-38 were investigated and compared with responses to PACAP-27 and vasoactive intestinal polypeptide (VIP) in the pulmonary vascular bed of the intact-chest cat under constant flow condi ... Full text Link to item Cite

Analysis of responses to serotonin in the pulmonary vascular bed of the cat.

Journal Article J Appl Physiol (1985) · July 1993 Pulmonary vascular responses to serotonin (5-hydroxytryptamine; 5-HT) were investigated in the intact-chest cat under constant-flow conditions. Injections of 5-HT into the perfused lobar artery in doses of 1-30 micrograms caused dose-related increases in l ... Full text Link to item Cite

Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed.

Journal Article J Appl Physiol (1985) · April 1993 Featured Publication The influence of Zaprinast (M&B 22948), a guanosine 3',5'-cyclic monophosphate (cGMP)-specific phosphodiesterase inhibitor, was investigated in the pulmonary vascular bed of the cat under conditions of controlled blood flow and constant left atrial pressur ... Full text Link to item Cite

Analysis of responses to substance P in the pulmonary vascular bed of the cat.

Journal Article Am J Physiol · February 1993 Responses to substance P were investigated in the pulmonary vascular bed of the cat with controlled pulmonary blood flow and constant left atrial pressure. Under baseline conditions, intralobar injections of substance P caused small, inconsistent reduction ... Full text Link to item Cite

Analysis of systemic and pulmonary vascular responses to PACAP and VIP: role of adrenal catecholamines.

Journal Article Am J Physiol · December 1992 Systemic and pulmonary vascular responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with 68% sequence homology to vasoactive intestinal peptide (VIP), were investigated in the anesthetized cat. Intravenous injections of ... Full text Link to item Cite

Methylene blue inhibits neurogenic cholinergic vasodilator responses in the pulmonary vascular bed of the cat.

Journal Article Am J Physiol · November 1992 The effects of methylene blue, an inhibitor of soluble guanylate cyclase, on pulmonary vasodilator responses to efferent vagal stimulation were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure ... Full text Link to item Cite

Analysis of responses to big endothelin in the hindquarters vascular bed of the cat.

Journal Article Can J Cardiol · November 1992 OBJECTIVE: To investigate vascular responses to the endothelin-1 (ET-1) precursor, human big endothelin 1-38 (big ET), in the peripheral vascular bed of the cat. DESIGN: These studies were designed to investigate the hypothesis that bit ET is converted to ... Link to item Cite

Inhibitory effects of DuP 753 and EXP3174 on responses to angiotensin II in pulmonary vascular bed of the cat.

Journal Article J Appl Physiol (1985) · November 1992 The effects of the non-peptide antagonist DuP 753 and its metabolite EXP3174 on responses to angiotensin II were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure ... Full text Link to item Cite

Analysis of pulmonary and systemic vascular responses to platelet-activating factor in the cat.

Journal Article Am J Physiol · July 1992 Pulmonary and systemic vascular responses to platelet-activating factor (PAF) were investigated in the anesthetized cat. Intravenous injections of PAF decreased arterial pressure, increased pulmonary arterial pressure, and caused small but significant decr ... Full text Link to item Cite

Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat.

Journal Article J Appl Physiol (1985) · June 1992 The influence of daltroban (BM13.505; SK&F 96148), a thromboxane (Tx) A2-receptor-blocking agent, on responses to the TxA2 mimics U-46619 and U-44069 was investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. Dal ... Full text Link to item Cite

Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary vascular bed of the cat by sulotroban.

Journal Article Eur J Pharmacol · March 17, 1992 The effects of sulotroban (BM13.177; SK & F 95587), a thromboxane (TX) A2/endoperoxide (PGH2) receptor blocking agent on responses to the TXA2/PGH2 mimics, U46619 and U44069, were investigated in the pulmonary vascular bed of the intact-chest cat under con ... Full text Link to item Cite

Differential effects of PACAP and VIP on the pulmonary and hindquarters vascular beds of the cat.

Journal Article J Appl Physiol (1985) · March 1992 Responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide derived from ovine hypothalamus with 68% sequence homology with vasoactive intestinal polypeptide (VIP), were investigated in the pulmonary and hindquarters vascular b ... Full text Link to item Cite

Characterization of thromboxane receptor blocking effects of SQ 29548 in the feline pulmonary vascular bed.

Journal Article J Appl Physiol (1985) · March 1992 The effects of SQ 29548, a thromboxane (Tx) A2 receptor blocking agent, on responses to the TxA2 mimic U46619 were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 29548 in doses of ... Full text Link to item Cite

Pulmonary vasodilator response to vagal stimulation is blocked by N omega-nitro-L-arginine methyl ester in the cat.

Journal Article Circ Res · February 1992 Featured Publication The effect of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor production, on the vasodilator response to efferent vagal stimulation was investigated in the pulmonary vascular bed of the intact-chest cat u ... Full text Link to item Cite

N omega-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin.

Journal Article J Appl Physiol (1985) · November 1991 Featured Publication The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact-chest cat under conditions of ... Full text Link to item Cite

Analysis of responses to sarafotoxin 6a and sarafotoxin 6c in the pulmonary vascular bed of the cat.

Journal Article J Appl Physiol (1985) · November 1991 Pulmonary vascular responses to sarafotoxins 6a and 6c (S6a and S6c) were investigated in the intact-chest cat under constant flow conditions. Injections of S6a and S6c into the perfused lobar artery caused dose-related increases in lobar arterial pressure ... Full text Link to item Cite

Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed.

Journal Article J Appl Physiol (1985) · November 1991 The effects of SQ 30741, a thromboxane A2 (TxA2) receptor blocking agent, on responses to the TxA2 mimic, U-46619, were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 30741 in dos ... Full text Link to item Cite

Influence of SQ 29,548 on vasoconstrictor responses in the hindquarters vascular bed of the cat.

Journal Article Prostaglandins Leukot Essent Fatty Acids · October 1991 The effects of SQ 29,548, a thromboxane (TX) receptor blocking agent, on vasoconstrictor responses were investigated under conditions of controlled blood flow in the hindquarters vascular bed of the cat. Intravenous injection of SQ 29,548 at a dose of 0.1 ... Full text Link to item Cite

Influence of lemakalim on the pulmonary vascular bed of the cat.

Journal Article Eur J Pharmacol · September 4, 1991 Pulmonary vascular responses to the K+ATP channel opener, lemakalim, were investigated in the intact-chest cat under constant flow conditions. When tone in the pulmonary vascular bed was elevated, intralobar injections of lemakalim caused dose-related decr ... Full text Link to item Cite

Pulmonary vasodilator responses to RP 52891 are mediated by activation of a glibenclamide-sensitive K+ATP channel.

Journal Article Eur J Pharmacol · September 4, 1991 Pulmonary vasodilator responses to the K+ATP channel opener, RP 52891, were investigated in the intact-chest cat under constant flow conditions. When pulmonary vascular tone was increased with U46619, intralobar injections of RP 52891 caused dose-related d ... Full text Link to item Cite

Pulmonary vascular and airway responses to endothelin-1 are mediated by different mechanisms in the cat.

Journal Article J Cardiovasc Pharmacol · 1991 The role of cyclooxygenase product formation and thromboxane A2 receptor activation in the response to endothelin-1 (ET-1) was investigated and compared in the airways and in the pulmonary vascular bed of the intact-chest cat. Intravenous injections of ET- ... Full text Link to item Cite

N(ω)-nitro-L-arginine methyl ester selectively inhibits pulmonary vasodilator responses to acetylcholine and bradykinin

Journal Article Journal of Applied Physiology · January 1, 1991 The effects of N(ω)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor (EDRF) production, on vascular tone and responses were investigated in the pulmonary vascular bed of the intact- chest cat under conditions of c ... Cite