RENAL AND HEMODYNAMIC-RESPONSES TO A NOVEL KAPPA-OPIOID RECEPTOR AGONIST, NIRAVOLINE (RU-51,599) IN RATS WITH CIRRHOSIS

Because renal water retention is a complication of cirrhosis, niravoli ne (RU 51,599), a novel kappa (kappa) opioid receptor agonist which is known to cause a water diuresis under normal conditions, may be usefu l in the therapy of chronic liver diseases. Thus, the present study ex amined the effects of niravoline on renal function in rats with cirrho sis. Urine was collected during the 2 h period following the administr ation of vehicle (saline) in one group of animals or niravoline (3 mg/ kg, i.v.) in another group. Urinary and plasma osmolality were measure d prior to and 2 h after niravoline in a third group of animals. Urine flow and natraemia were significantly higher after niravoline (147 +/ - 12 mu L/min and 153 +/- 2 mmol/L, respectively) than after vehicle ( 27 +/- 7 mu L/min and 146 +/- 1 mmol/L, respectively). Niravoline sign ificantly decreased urinary osmolality and significantly increased pla sma osmolality and free water clearance. This substance did not signif icantly change urinary sodium excretion. In conclusion, this study sho ws that niravoline, a kappa opioid receptor agonist, induced a water d iuresis in rats with cirrhosis.