Pharmacological analysis of positive chrono- and inotropic responses to denopamine (TA-064) in dog cross-circulated atrial and ventricular preparations.
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, blood-perfused dog heart preparations, and they also suggest a mild catecholamine-releasing activity through tyramine-like action in isolated right atria.
Akahane
K
K
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Karasawa
Y
Y
Ren
L M
LM
Chiba
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003427:Cross Circulation; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D004983:Ethanolamines; D011412:Propanolamines; C026777:ICI 118551; D001262:Atenolol; D007545:Isoproterenol; D007099:Imipramine; C037293:denopamine; D009638:Norepinephrine; D017265:Procaterol