INTERACTION BETWEEN ANGIOTENSIN-II AND NITRIC-OXIDE IN CONTROL OF RENAL HEMODYNAMICS IN CONSCIOUS DOGS

Recent in vitro studies have provided evidence that the vasoconstrictor actions of angiotensin II on afferent arterioles are enhanced by nitric oxide synthesis inhibition. Although these studies suggest that nitric oxide may play a role in protecting the afferent arterioles from angiotensin II-induced vasoconstriction, the importance of this interaction in the regulation of glomerular filtration rate and renal blood flow in the intact, conscious animal is not known. The objective of the present study was to determine the role of nitric oxide in modulating the renal hemodynamic and excretory effects of angiotensin II. Angiotensin II was infused at rates of 0.5, 1.0, and 2.0 mu g.kg(-1).min(-1) intrarenally in conscious, chronically instrumented dogs in both the presence and absence of nitric oxide synthesis inhibition by continuous intrarenal infusion of N-G-nitro-L-arginine methyl ester (3 mu g.kg(-1) min(-1)). At a dose of 0.5 mu g.kg(-1).min(-1), angiotensin II decreased renal plasma flow by 19%, while having no effect on glomerular filtration rate in control dogs. In contrast, angiotensin II decreased renal plasma flow by 54%, glomerular filtration rate by 40%, and increased renal vascular resistance by 125% in the presence of intrarenal nitric oxide synthesis blockade. At doses of 1.0 and 2.0 mu g kg(-1) min(-1), angiotensin II reduced renal plasma flow by 36 and 45%, glomerular filtration rate by 17 and 23%, and increased renal vascular resistance by 80 and 120%, respectively, in control dogs. In the presence of nitric oxide synthesis blockade, doses of 1.0 and 2.0 mu g.kg(-1).min(-1) of angiotensin II decreased renal plasma flow by 62 and 70%, glomerular filtration rate by 45 and 55%, and increased renal vascular resistance by 186 and 285%, respectively. Angiotensin II-induced reductions in fractional excretion of sodium and lithium were also enhanced by nitric oxide synthase inhibition. These findings suggest that nitric oxide plays an important role in the regulation of renal hemodynamics and electrolyte excretion by modulating the renal vasoconstrictor actions of angiotensin II.