Jpn. J. Pharmacol. 72, 325-333 (1996)

Prolongation of the Life Span of Cardiomyopathic Hamster by the Adrenergic beta1-Selective Partial Agonist Denopamine

Hideo Kurosawa (1), Hiroshi Narita (2,*), Minako Kaburaki (2), Hideo Yabana (1), Hisayoshi Doi (2), Emiko Itogawa (1) and Masahito Okamoto (2)

(1) Lead Optimization Research Laboratory and (2) Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50 Toda, Saitama 335, Japan
(*) To whom correspondence should be addressed.

Abstract: Influence of cardiotonic agents on the prognosis of heart failure depends on the individual therapeutic agents, and favorable and unfavorable effects of these agents have been reported in clinical trials. We studied the effect of the cardiotonic agent denopamine on the life span of cardiomyopathic hamsters (BIO 14.6 strain) in the heart failure period. Non-treated hamsters started to die at 40 weeks of age, and their survival rate decreased to 23.8% at the age of 65 weeks. Hamsters treated with denopamine (400 ppm in diet) from 36 weeks of age did not die until the age of 52 weeks, except in cases of accidental death. The survival rate of this group at 65 weeks of age was about 40%. Survival rates of these 2 groups were significantly different (P < 0.05) when animals with accidental death were excluded. To elucidate the mechanism of the effect of denopamine, we performed several experiments after dietary treatment with denopamine for 4 to 6 weeks from 37 weeks of age. Denopamine treatment lowered plasma levels of noradrenaline and dopamine (P < 0.05), but affected neither the cardiac contractility nor the beta-adrenoceptor density. In summary, denopamine significantly decreases the mortality of cardiomyopathic hamsters. Its effect to lower the plasma catecholamine levels may be responsible for the beneficial effect of denopamine.

Keywords: Denopamine, Cardiomyopathic hamster, Prognosis, Congestive heart failure, Plasma catecholamine level