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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sparks, MA; Stegbauer, J; Chen, D; Gomez, JA; Griffiths, RC; Azad, HA; Herrera, M; Gurley, SB; Coffman, TM

Published Date

  • December 2015

Published In

Volume / Issue

  • 26 / 12

Start / End Page

  • 2953 - 2962

PubMed ID

  • 25855778

Pubmed Central ID

  • 25855778

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

International Standard Serial Number (ISSN)

  • 1046-6673

Digital Object Identifier (DOI)

  • 10.1681/ASN.2014080816

Language

  • eng