Item Type: | Article |
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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., Buergelova, M., Vaneckova, I., Vanourkova, Z., Huskova, Z., Skaroupkova, P., Mrazova, I., Opocensky, M., Kramer, H.J., Netuka, I., Maly, J., Alenina, N., Bader, M., 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 |
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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