Sustained aquaretic effect of the V 2 ‐AVP receptor antagonist, RWJ‐351647, in cirrhotic rats with ascites and water retention

A disturbance in body water homeostasis is a common feature in advanced cirrhosis. This disturbance is always associated with the existence of ascites and is characterized by an inability to adjust the amount of water excreted in the urine to the amount of water ingested. Vasopressin (AVP) is of major importance in the pathogenesis of water retention and hyponatremia in cirrhosis. The current study assessed the renal, hormonal and hemodynamic effects induced by 10‐day chronic oral administration of RWJ‐351647 (0.5 mg kg −1 daily), a new nonpeptide V 2 ‐AVP antagonist, in rats with CCl 4 ‐induced cirrhosis, ascites and severe water retention. Urine volume (UV), urine osmolality and sodium and potassium excretion were measured daily. At the end of the study, systemic hemodynamic parameters were also assessed. Long‐term administration of RWJ‐351647 has an aquaretic effect in rats with cirrhosis, ascites, water retention and hypo‐osmolality. It increases UV (ANOVA: F =7.32, P