| Co-Investigator(Kenkyū-buntansha) |
KUROSAWA Hideo Tanabe Seiyaku, Biol.Res.Lab., 医薬育成研究所, 主任研究員
YAMADA Hiroaki Nisshin Flour Milling, Pharmaceutical Res.Lab., 生物研究所, 主任研究員
SATO Yasufumi Tohoku University, Inst.Aging & Development, Professor, 加齢医学研究所, 教授 (50178779)
SUKEGAWA Jun Tohoku University, Sch.Med., Dept.Pharmacol., Lecturer, 医学部, 講師 (30187687)
NUNOKI Kazuo Tohoku University, Sch.Med., Dept.Pharmacol., Lecturer, 医学部, 講師 (10172743)
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| Research Abstract |
In isolated canine right ventricular muscles, we investigated the differences in antagonisms by beta-blockers against the positive inotropic effects (PIEs) of isoproterenol, a nonselective agonist, and T-0509, a beta1-selective agonist. The selective beta1-blockers atenolol or bisoprolol, and nadolol, a nonselective beta-blocker antagonized the PIE of T-0509 monophasically in Schild analysis, showing pA2 values of 7.05,7.63, and 7.58, respectively. On the other hand, both blockers produced biphasic antagonism against the PIE of isoproterenol (ISO) ; therefore, two pKB values were obtained (7.75 and 4.25 ; 7.82 and 5.76 ; 7.42 and 4.39, respectively). Because the different mode of antagonism by three beta-blockers between T-0509 and ISO could not be explained by the selectivities of beta-agonists and blockers for beta1- and beta2-adrenoceptors in the heart, two subtypes of beta1-adrenoceptors may exist together in canine ventricular muscles, and atenolol, bisoprolol, and nadolol may act as antagonists for the two subtypes (beta1- and atypical beta- or beta3-adrenoceptors) with two different affinities.
The influences were investigated of denopamine, beta1-adrenoceptor partial agonist, on the life span of cardiomyopathic hamsters (BIO 14.6 strain) in the heart failure period. The survival rate of denopamine group at 65 weeks of age was higher than control group. 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.
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