Comparison of two aquaretic drugs (Niravoline and OPC-31260) in cirrhotic rats with ascites and water retention

kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic horm one (ADH) V-2 receptor antagonists (OPC-31260) possess aquaretic activity i n cirrhosis; however, there is no information concerning the effects induce d by the chronic administration of these drugs under this condition. To com pare the renal and hormonal effects induced by the long-term oral administr ation of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolalit y, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH wer e measured in basal conditions and for 10 days after the daily oral adminis tration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expr ession, and systemic hemodynamics were also measured at the end of the stud y. Niravoline increased water excretion, peripheral resistance, serum osmol ality, and sodium excretion and reduced creatinine clearance, ALD and ADH e xcretion, and mRNA expression of ADH. OPC-31260 also increased water metabo lism and sodium excretion and reduced urinary ALD, although the aquaretic e ffect was only evident during the first 2 days, and no effects on serum osm olality, renal filtration, and systemic hemodynamics were observed. Therefo re, both agents have aquaretic efficacy, but the beneficial therapeutic eff ects of the long-term oral administration of niravoline are more consistent than those of OPC-37260 in cirrhotic rats with ascites and water retention .