Vascular type 1A angiotensin II receptors control BP by regulating renal blood flow and urinary sodium excretion

Matthew A. Sparks, Johannes Stegbauer, Daian Chen, Jose A. Gomez, Robert C. Griffiths, Hooman A. Azad, Marcela Herrera, Susan Gurley, Thomas M. Coffman

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19 Scopus citations

Abstract

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 generatedmicewith cell-specific deletion ofAT1A 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 vasculaturewere largely preserved (approximately 80% of control levels) in SMKOmice 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 circulationwere 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.

Original languageEnglish (US)
Pages (from-to)2953-2962
Number of pages10
JournalJournal of the American Society of Nephrology
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

Cite this

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. Journal of the American Society of Nephrology, 26(12), 2953-2962. https://doi.org/10.1681/ASN.2014080816