Effect of the V1a/V2-AVP receptor antagonist, Conivaptan, on renal water metabolism and systemic hemodynamics in rats with cirrhosis and ascites

Background: Selective V2-AVP receptor antagonists are effective in inducing aquaresis in humans and rats with cirrhosis, hyponatremia and water retention. However, it is unknown whether dual V1a/V2-AVP antagonists are also efficacious as aquaretic agents under these conditions. This is important, particularly considering that blockade of V1a-AVP receptors could aggravate cardiocirculatory function in decompensated cirrhosis. Aims: To evaluate the renal, hormonal and hemodynamic effects induced by the chronic oral administration of the V1a/V2-AVP antagonist, Conivaptan, in rats with CCl4-induced cirrhosis, ascites and severe water retention. Methods: We assessed the aquaretic efficacy of 10-day chronic oral administration of Conivaptan (0.5 mg/kg body weight (bw)) in cirrhotic rats with hyponatremia and water retention. Urine volume (UV), osmolality (UOsm), and sodium excretion (UNaV) were measured daily. At the end of the study arterial pressure was also measured. Results: Conivaptan produced an acute increase in UV, a reduction in UOsm and, at the end of the investigation, cirrhotic rats receiving the V1a/V2-AVP receptor antagonist did not show hyponatremia or hypoosmolality. Conivaptan also normalized UNaV without affecting creatinine clearance and arterial pressure. Conclusions: Dual V1a/V2-receptor antagonists may be therapeutically useful for the treatment of water retention and dilutional hyponatremia in human cirrhosis.