Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V-1A and V-2 receptor antagonist, in dogs with pacing-induced congestive heart failure

The systemic hemodynamic and renal responses to conivaptan hydrochloride (Y M087; 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbon yl)-2-phenylbenzanilide monohydrochloride), a vasopressin V-1A and V-2 rece ptor antagonist, were determined in pentobarbital-anesthetized dogs after 3 , to 3 weeks of rapid right ventricular pacing. Congestive heart failure, c haracterized by decreases in first derivative of left ventricular pressure (left ventricular d P/dt(max)) and cardiac output, and increases in left ve ntricular end-diastolic pressure and total peripheral vascular resistance, was induced by chronic rapid right ventricular pacing at 260-280 beats/min. Intravenous administration of conivaptan (0.1 mg/kg) significantly increas ed left ventricular dP/dt(max) and cardiac output and significantly decreas ed left ventricular end-diastolic pressure and total peripheral vascular re sistance. Conivaptan also increased urine flow and reduced urine osmolality by markedly increasing free water clearance. These results indicate that c onivaptan produced hemodynamic improvement and marked aquaresis in dogs wit h congestive heart failure. Therefore, conivaptan may find clinical use in treating patients with congestive heart failure. (C) 1999 Elsevier Science B.V. All rights reserved.