TY - JOUR T1 - Comparison of Two Aquaretic Drugs (Niravoline and OPC-31260) in Cirrhotic Rats with Ascites and Water Retention JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 194 LP - 201 VL - 289 IS - 1 AU - Marta Bosch-Marcé AU - Jorge-Luis Poo AU - Wladimiro Jiménez AU - Nuria Bordas AU - Alberto Leivas AU - Manuel Morales-Ruiz AU - Rosa Maria Muñoz AU - Manuel Pérez AU - Vicente Arroyo AU - Francisca Rivera AU - Juan Rodés Y1 - 1999/04/01 UR - http://jpet.aspetjournals.org/content/289/1/194.abstract N2 - κ-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention. The American Society for Pharmacology and Experimental Therapeutics ER -