Therapeutic efficacy of the non-peptide AVP antagonist OPC-31260 in cirrhotic rats.

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist [5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine] (OPC-31260) improves the impaired water excretion in rats with experimental liver cirrhosis. Male Wistar rats weighing 200 to 250 g were injected in an equal volume (4 ml/kg) of carbon tetrachloride and olive oil at an interval of seven days for three months, causing liver cirrhosis with ascites. Control rats were injected with only olive oil. Body weight (body wt) and hematocrit (Hct) were lower in the cirrhotic rats than the control rats (body wt 360.7 vs. 238.5 g, P < 0.01; Hct 46.3 vs. 39.2%, P < 0.01). A water loading test (30 ml/kg) was carried out and 20-minute urine collections were made for three hours. The percent of water load excreted was 62.5% in the cirrhotic rats, a value significantly less than that of 102.1% in the control rats. However, its percent increased to 215.1% after the oral administration of 5 mg/kg OPC-31260 (P < 0.01). Minimal urinary osmolality (UOsm) was 185.5 mOsm/kg H2O in the cirrhotic rats receiving the vehicle, a value greater than the control rats of 125.5 mOsm/kg H2O (P < 0.01). The oral administration of 5 mg/kg OPC-31260 reduced minimal UOsm to 85.2 mOsm/kg H2O in the cirrhotic rats (P < 0.01). Urinary excretion of sodium was lower in the cirrhotic rats than the control rats (87.1 vs. 312.4 microEq/3 hr, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)