Renal effects of piretanide in dogs

Effects of 4-phenoxy-3-(1-pyrrolidinyl)-5-sulfamoyl benzoic acid (piretanide, Arelix) on renal function and hemodynamics were investigated in anesthetized dogs by clearance, stop-flow and radioactive microsphere methods. Marked diuresis occurred within 10 min after intravenous injection of piretanide (0.01, 0.05 and 0.25 mg/kg) and it was accompanied b natriuresis. Piretanide (0.25 mg/kg) clearly inhibited the reabsorption of solute-free water during saline diuresis, suggesting that the drug acts in the ascending limb of Henle's loop. Stop-flow experiments revealed that sodium reabsorption was reduced by piretanide (0.25 mg/kg) at the distal tubule including the ascending limb of Henle's loop. Piretanide (0.25 mg/kg) caused a maximum increase of about 30% in renal blood flow at 10-15 min after the injection; within the renal cortex the increase in blood flow was greater in the juxtamedullary area than in the superficial area. The increased blood flow in the inner cortex conceivably resulted in a washout of the osmotic substances in the medulla and inhibited the concentrating mechanisms of the kidney. The effect of piretanide on intrarenal hemodynamics may also contribute to its diuretic action.