Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure.
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 V1A and V2 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/dt(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 dP/dt(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.
Yatsu
T
T
Cardiovascular Diseases Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan. yatsu@yamanouchi.co.jp
Tomura
Y
Y
Tahara
A
A
Wada
K
K
Kusayama
T
T
Tsukada
J
J
Tokioka
T
T
Uchida
W
W
Inagaki
O
O
Iizumi
Y
Y
Tanaka
A
A
Honda
K
K
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use* / Q000652:urine; D002304:Cardiac Pacing, Artificial; D002317:Cardiovascular Agents / Q000627:therapeutic use* / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D017483:Receptors, Vasopressin / Q000627:therapeutic use*; D012076:Renal Agents / Q000627:therapeutic use* / Q000652:urine
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D002317:Cardiovascular Agents; D017483:Receptors, Vasopressin; D012076:Renal Agents; C106389:conivaptan