Angiotensin-(1-7)-induced renal vasodilation is reduced in human kidneys with renal artery stenosis

BACKGROUND:Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin–angiotensin system. As the renin–angiotensin system is also activated in kidneys with renal artery stenosis, we hypothesized that the vasodilatory effect of angiotensin-(1-7) is also reduced in such kidneys. METHOD:Therefore, we selectively measured mean renal blood flow (Xenon washout method) before and during local infusion of angiotensin-(1-7) (0.27, 0.9, and 2.7 ng/kg per min) in hypertensive patients who were angiographically evaluated for the presence of renovascular abnormalities. Data were analyzed in three groupsstenotic kidneys, nonstenotic kidneys with renal artery stenosis of the contralateral kidney (contralateral stenotic kidneys), or essentially hypertensive controls without renovascular abnormalities (matched for urinary sodium excretion). RESULTS:Angiotensin-(1-7) infusion resulted in an increase in renal blood flow in matched controls. In stenotic kidneys however, the effect of angiotensin-(1-7) was significantly reduced as compared to controls. The angiotensin-(1-7) effect in contralateral stenotic kidneys was comparable to controls. CONCLUSION:Angiotensin-(1-7)-induced vasodilation is reduced in stenotic kidneys, but not in contralateral stenotic kidneys. This suggests that the altered blood flow regulation in kidneys with atherosclerotic renal artery stenosis is a local phenomenon and not related to generalized atherosclerotic burden. Probably, the renin–angiotensin system activation, bioavailability of nitric oxide, and structural changes in the stenotic kidney play a role in this phenomenon.