Modification by diazoxide of canine renal vascular responsiveness to endogenous vasoconstrictors

Abstract

Diazoxide-induced modification of renal vascular responses to norepinephrine and angiotensin II was studied in dogs. Diazoxide was infused directly into the renal artery in order to minimize the effect of high plasma protein binding and to obtain maximum exposure of the test vessel to the administered drug. During the 30-min infusion period, renal blood flow showed an initial, transitory increase followed by a progressive decline which paralleled the induced fall in systemic blood pressure. In the presence of diazoxide, renal vasoconstrictor responses to intravenous and intraarterial norepinephrine and intravenous angiotensin II were significantly attenuated. In contrast, the renal vasoconstrictor response to intraarterial angiotensin II was not significantly modified by diazoxide. This differential inhibition by diazoxide of renal vasoconstriction to norepinephrine or angiotensin I 1 may warrant consideration when these pressor agents are being used to overcome the excessive hypotension resulting from inadvertent diazoxide overdosage.