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

Abstract

The systemic hemodynamic and renal responses to conivaptan hydrochloride (YM087; 4′-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5- d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a vasopressin V 1A and V 2 receptor antagonist, were determined in pentobarbital-anesthetized dogs after 2 to 3 weeks of rapid right ventricular pacing. Congestive heart failure, characterized by decreases in first derivative of left ventricular pressure (left ventricular d P/d t max) and cardiac output, and increases in left ventricular 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 increased left ventricular d P/d t max and cardiac output and significantly decreased left ventricular end-diastolic pressure and total peripheral vascular resistance. Conivaptan also increased urine flow and reduced urine osmolality by markedly increasing free water clearance. These results indicate that conivaptan produced hemodynamic improvement and marked aquaresis in dogs with congestive heart failure. Therefore, conivaptan may find clinical use in treating patients with congestive heart failure.