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.
2010 S. Karger AG, Basel.