Diuretic effect induced by intrarenal infusion of pinacidil in anesthetized dogs

The diuretic action of pinacidil, a new vasodilating antihypertensive agent, was studied using anesthetized dogs. Intrarenally administered pinacidil (0.4, 2.0 and 10 micrograms/kg/min) produced a dose-related increase of renal blood flow, without altering mean arterial pressure. The glomerular filtration rate significantly increased only with the highest dosage. Pinacidil caused a dose-related augmentation of urine formation and, when given at 10 micrograms/kg/min, increased urine flow and urinary excretion of electrolytes to about 10 times and 3 to 9 times over the respective control value. In comparison, hydralazine (4.0 and 20 micrograms/kg/min) produced no significant diuretic action and bradykinin, given at a dose (0.02 micrograms/kg/min) equipotent to pinacidil (10 micrograms/kg/min) with respect to increasing renal blood flow, was less effective. Pinacidil administration significantly increased the fractional excretion of phosphate. Thus, pinacidil-induced diuresis seems to be due mainly to the vasodilating effect on renal vessels, with some contribution from an inhibitory effect on sodium reabsorption in the proximal tubules.