Pharmacological analysis of positive chrono- and inotropic responses to denopamine (TA-064) in dog cross-circulated atrial and ventricular preparations.

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Positive chrono and inotropic responses to denopamine (TA-064, (-)(R)-1-(p-hydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl)amino] ethanol), a new and orally active cardiotonic agent, were investigated in the canine isolated right atrial or left ventricular preparation which was cross-circulated with blood from another support dog. Denopamine dose-dependently increased the sinus rate, right atrial and left ventricular contractile force. Denopamine was one to two orders of magnitude less potent than isoproterenol. The positive chrono and inotropic effects of denopamine in isolated, blood-perfused right atria were dose-dependently inhibited by treatment with propranolol and atenolol. The effects of denopamine were only slightly attenuated by ICI 118, 551 in doses which completely suppressed the positive chrono and inotropic effects of procaterol. The increases in sinus rate and atrial contractility induced by denopamine were partially but significantly attenuated by treatment with imipramine in a dose which suppressed the effects of tyramine and potentiated the effects of norepinephrine. These results indicate that denopamine is a highly selective beta-1 adrenoceptor agonist in isolated, bloodperfused dog heart preparations, and they also suggest a mild catecholaminereleasing activity through tyramine-like action in isolated right atria.