RENAL EFFECTS OF THE CALCIUM-CHANNEL BLOCKER ARANIDIPINE AND ITS ACTIVE METABOLITE IN ANESTHETIZED DOGS AND CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

The purpose of this study was to investigate the renal effects of aran idipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneo usly hypertensive rats (SHRs). When infused into the renal artery in a nesthetized dogs, aranidipine (0.03 mu g/kg/min) induced sustained inc reases in urine volume and urinary excretion of sodium and of potassiu m. This effect was greater than that elicited by nifedipine (0.1 mu g/ kg/min). The aranidipine metabolite, M-1 (0.1 mu g/kg/min), also cause d diuresis and natriuresis almost equal to those of nifedipine. The st op-flow experiment using the anesthetized dog showed that intrarenal i nfusion of aranidipine (0.03 mu g/kg/min), as well as nifedipine (0.1 mu g/kg/min), produced natriuresis at the distal tubular site rather t han at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when admi nistered orally, dose-dependently increased urine volume and urinary e xcretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/k g, p.o.) also showed diuretic and natriuretic effects comparable to th ose of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was no t found for its diuretic and natriuretic effects in SHRs. These result s suggest that, apart from antihypertensive efficiency, aranidipine ma y offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute , in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.