Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure

被引：60

作者：

Yatsu, T ^{[1
]}

Tomura, Y ^{[1
]}

Tahara, A ^{[1
]}

Wada, K ^{[1
]}

Kusayama, T ^{[1
]}

Tsukada, J ^{[1
]}

Tokioka, T ^{[1
]}

Uchida, W ^{[1
]}

Inagaki, O ^{[1
]}

Iizumi, Y ^{[1
]}

Tanaka, A ^{[1
]}

Honda, K ^{[1
]}

机构：

[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Pharmacol Labs, Cardiovasc Dis Res, Tsukuba, Ibaraki 3058585, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 376卷 / 03期

关键词：

conivaptan hydrochloride; congestive heart failure; vasopressin receptor antagonist; non-peptide; vasoconstriction; water retention;

D O I：

10.1016/S0014-2999(99)00379-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 3, 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. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：239 / 246

页数：8

共 41 条

[1] RAPID VENTRICULAR PACING IN THE DOG - PATHOPHYSIOLOGIC STUDIES OF HEART-FAILURE [J].