Diuretic effect induced by intrarenal infusion of nisoldipine in anaesthetized dogs.

1. Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of nisoldipine (10, 50 ng/kg per min) did not influence mean systemic blood pressure and renal haemodynamics, but did cause dose-related increases in urine flow and urinary excretion of electrolytes. During nisoldipine infusion at the higher dose, the levels of fractional excretion of sodium, potassium and chloride were significantly elevated. 3. In the lithium clearance study, fractional lithium excretion, an index of fractional sodium excretion in the proximal tubules, was unchanged even with the higher dose of nisoldipine, whereas fractional sodium excretion in the distal tubules markedly increased. 4. Nisoldipine elicited a significant increment in osmolar clearance without altering the reabsorption of free water. 5. Thus, intrarenal administration of nisoldipine at a non-hypotensive dose to anaesthetized dogs produced a significant diuretic effect without alteration in renal haemodynamics. Results in lithium clearance and free water clearance studies suggest that nisoldipine exerts a diuretic action by inhibiting sodium transport at the distal nephron segments beyond the proximal tubules.