Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II
Open Access
- 10 November 2010
- journal article
- research article
- Published by S. Karger AG in Kidney and Blood Pressure Research
- Vol. 33 (6), 476-488
- https://doi.org/10.1159/000320689
Abstract
Aims: The present study was performed to evaluate the effects of target disruption of the G-protein-coupled receptor Mas for angiotensin 1–7 [Ang(1–7)] in knockout mice on the course of two-kidney, one-clip (2K1C) Goldblatt hypertension. Methods: Knockout and wild-type mice underwent clipping of one renal artery. Blood pressure (BP) was monitored by radiotelemetry. The mice were either untreated or chronically treated with the superoxide (O2–) scavenger tempol (400 mg/l) or the inhibitor of NADPH oxidase apocynin (1 g/l) administered in drinking water. Results: Knockout mice responded to clipping by accelerated increases in BP and the final BP was significantly higher than that in wild-type mice. Chronic treatment with tempol or apocynin elicited similar antihypertensive effects in 2K1C/knockout as in 2K1C/wild-type mice. Acute nitric oxide synthase inhibition caused greater BP increases in 2K1C/wild-type than in 2K1C/knockout mice. Conclusion: Our present findings support the notion that the angiotensin-converting enzyme 2-Ang(1–7)-Mas axis serves as an important endogenous physiological counterbalancing mechanism that partially attenuates the hypertensinogenic actions of the activated renin-angiotensin system. The impairment in this axis may contribute to the deterioration of the course of 2K1C Goldblatt hypertension.Keywords
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