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

Publication ,  Journal Article
Sparks, MA; Stegbauer, J; Chen, D; Gomez, JA; Griffiths, RC; Azad, HA; Herrera, M; Gurley, SB; Coffman, TM
Published in: 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, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control.

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Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 2015

Volume

26

Issue

12

Start / End Page

2953 / 2962

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Vasoconstriction
  • Urology & Nephrology
  • Sympathetic Nervous System
  • Renal Circulation
  • Receptor, Angiotensin, Type 1
  • Phentolamine
  • Natriuresis
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
 

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Sparks, M. A., Stegbauer, J., Chen, D., Gomez, J. A., Griffiths, R. C., Azad, H. A., … Coffman, T. M. (2015). Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion. J Am Soc Nephrol, 26(12), 2953–2962. https://doi.org/10.1681/ASN.2014080816
Sparks, Matthew A., Johannes Stegbauer, Daian Chen, Jose A. Gomez, Robert C. Griffiths, Hooman A. Azad, Marcela Herrera, Susan B. Gurley, and Thomas M. Coffman. “Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.J Am Soc Nephrol 26, no. 12 (December 2015): 2953–62. https://doi.org/10.1681/ASN.2014080816.
Sparks MA, Stegbauer J, Chen D, Gomez JA, Griffiths RC, Azad HA, et al. Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion. J Am Soc Nephrol. 2015 Dec;26(12):2953–62.
Sparks, Matthew A., et al. “Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.J Am Soc Nephrol, vol. 26, no. 12, Dec. 2015, pp. 2953–62. Pubmed, doi:10.1681/ASN.2014080816.
Sparks MA, Stegbauer J, Chen D, Gomez JA, Griffiths RC, Azad HA, Herrera M, Gurley SB, Coffman TM. Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion. J Am Soc Nephrol. 2015 Dec;26(12):2953–2962.

Published In

J Am Soc Nephrol

DOI

EISSN

1533-3450

Publication Date

December 2015

Volume

26

Issue

12

Start / End Page

2953 / 2962

Location

United States

Related Subject Headings

  • Vasoconstrictor Agents
  • Vasoconstriction
  • Urology & Nephrology
  • Sympathetic Nervous System
  • Renal Circulation
  • Receptor, Angiotensin, Type 1
  • Phentolamine
  • Natriuresis
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular