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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.
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