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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

Item Type:Article
Title: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
Creators Name:Rakusan, D. and Buergelova, M. and Vaneckova, I. and Vanourkova, Z. and Huskova, Z. and Skaroupkova, P. and Mrazova, I. and Opocensky, M. and Kramer, H.J. and Netuka, I. and Maly, J. and Alenina, N. and Bader, M. and Santos, R.A.S. and Cervenka, L.
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 (O(2)(-)) 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:Two-kidney, one-clip Goldblatt hypertension, Mas Receptor Knockout Mice, Nitric Oxide Deficiency, Animals, Mice
Source:Kidney and Blood Pressure Research
ISSN:1420-4096
Publisher:Karger (Switzerland)
Volume:33
Number:6
Page Range:476-488
Date:December 2010
Official Publication:https://doi.org/10.1159/000320689
PubMed:View item in PubMed

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