EFFECTS OF DILTIAZEM ON RENAL BLOOD FLOW AND RENAL FUNCTION DURING ANGIOTENSIN II INFUSION IN ANESTHETIZED DOGS

Abstract

Effects of diltiazem on renal blood flow and renal function were studied under angiotensin II-loaded condition in anesthetized dogs. Intravenous infusion of angiotensin II at a rate of 0.25 μg/kg/min produced an increase in blood pressure by 30 to 40 mmHg and a decrease in renal blood flow by 30 to 40%, resulting in a 100% increase in renal vascular resistance. Under this condition, diltiazem exhibited a dose related increase in renal blood flow not only by intrarenal administration (1-30 μg/kg) but also by intravenous administration (10-200 μg/kg). The effect was greatly augmented, compared to that observed in a control angiotensin II-unloaded condition. Under angiotensin II-loaded condition, glomerular filtration rate and para-aminohippuric acid clearance, as well as renal blood flow, were markedly reduced, the levels of which were recovered by intrarenal administration of diltiazem (10 μg/kg/min) accompanied by marked natriuresis. The natriuretic effect of diltiazem was also observed by intravenous administration (100 μg/kg). It is suggested that the improving effects diltiazem on renal hemodynamics and ranal function, under angiotensin II-loaded condition, are mainly due to its inhibitory action on angiotensin II-evoked renal vasoconstriction, resulting from its calcium antagonistic action.