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
T. Yatsu et al., 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, EUR J PHARM, 376(3), 1999, pp. 239-246
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.