Effect of the vasopressin receptor antagonist conivaptan in rats with heart failure following myocardial infarction

• Published in: European journal of pharmacology 2002-08, Vol.450 (2), p.169-177
• Main Authors: Wada, Koh-ichi, Tahara, Atsuo, Arai, Yukinori, Aoki, Motonori, Tomura, Yuichi, Tsukada, Junko, Yatsu, Takeyuki
• Format: Article
• Language: English
• Subjects: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines - pharmacology; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular system; Congestive heart failure; Conivaptan; Dose-Response Relationship, Drug; Heart; Heart Failure - etiology; Heart Failure - physiopathology; Heart Failure - prevention & control; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hemodynamics - drug effects; Male; Medical sciences; Myocardial Infarction - complications; Myocardial Infarction - pathology; Nonpeptide antagonist; Pharmacology. Drug treatments; Rats; Rats, Wistar; V 1A receptor; V 2 receptor; Vascular wall; Vasopressin; Vasopressins - blood
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02101-5

Myocardial infarction often induces congestive heart failure accompanied by a significant increase in plasma vasopressin concentration. To delineate the role of vasopressin in the pathogenesis of congestive heart failure, the acute hemodynamic and aquaretic effects of conivaptan (YM087, 4′-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5- d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a combined vasopressin V 1A and V 2 receptor antagonist, were assessed in rats with heart failure induced by myocardial infarction. Left coronary artery ligation resulted in decreased left ventricular systolic pressure and first derivatives of left ventricular developed pressure, as well as increased left ventricular end-diastolic pressure, lung and right ventricular weight. Single oral administration of conivaptan (0.3 to 3.0 mg/kg) dose-dependently increased urine volume and decreased urine osmolality in heart failure rats. Furthermore, conivaptan (3.0 mg/kg) attenuated the changes in left ventricular end-diastolic pressure, lung and right ventricular weight induced by heart failure while reducing blood pressure. These results show that vasopressin plays a significant role in elevating vascular tone through vasopressin V 1A receptors and plays a major role in retaining free water through vasopressin V 2 receptors in this model of congestive heart failure. Additionally, conivaptan, with its dual vasopressin V 1A and V 2 receptor-inhibiting properties, could exert a beneficial effect on cardiac function in the congestive heart failure rat model.