Effects of the highly selective kappa opioid, U-50, 488, on renal function in the anesthetized dog

Intravenous administration of U-50,488 (a chemically novel and highly selective kappa agonist) resulted in dose-dependent increases in urine formation in anesthetized dogs. The increase in urine formation was not accompanied by an increase in sodium or potassium excretion; thus, U-50,488 behaved like a water diuretic. In addition, a dose-dependent fall in blood pressure was noted after U-50,488 administration. Despite the effect on blood pressure, no changes in renal plasma flow (p-aminohippurate clearance) or glomerular filtration rate (inulin clearance) were detected at any dose tested. Apparently, the diuresis was primarily due to tubular effects and not to changes in renal hemodynamics. Intravenous infusion of antidiuretic hormone (2 pmol/min/kg) abolished completely the diuretic response to U-50,488 (5 mg/kg). This implied that the diuresis was mediated by an effect of the drug on antidiuretic hormone.