Acute nitric oxide blockade amplifies the renal vasoconstrictor actions of angiotension II.

The tone in the renal vasculature is determined by the balance between vasoconstrictor and vasodilator agents. In this study, the effect on renal function was investigated when the acute blockade of the endogenous nitric oxide system was superimposed on a state of high circulating angiotensin II. Studies were conducted in the conscious, unstressed rat measuring renal function before and during acute systemic nitric oxide blockade with nitro-L-arginine methyl ester and with or without concomitant angiotensin II infusion. Nitric oxide blockade alone, in the presence of normal, unstimulated levels of endogenous angiotensin II, caused a large rise in blood pressure and a doubling of renal vascular resistance. The infusion of angiotensin II alone produced a mild rise in systemic blood pressure and a small (30%) rise in renal vascular resistance. When nitric oxide blockade was combined with angiotensin II infusion, the rise in blood pressure was similar to that produced by nitric oxide blockade alone but the increase in renal vascular resistance was much greater (350%), leading to marked declines in renal function. These studies demonstrate that when angiotensin II levels are acutely elevated and are controlling renal vascular tone, nitric oxide is essential for the maintenance of adequate renal perfusion and function.