Positive chronotropic and inotropic effects of higenamine and its enhancing action on the aconitine-induced tachyarrhythmia in isolated murine atria.
Aconitine and higenamine are the components of aconite root. We investigated the cardiac effects of these compounds on murine right and left atria and the interaction of higenamine with aconitine on the rate of spontaneously beating right atria. Higenamine increased the rate (EC50 = 38 nM) and the force of contraction (EC50 = 97 nM), the maximal responses being comparable with those of isoproterenol. The positive chronotropic effect of higenamine was antagonized by propranolol (30-300 nM) and practolol (10 nM-3 microM), but not by butoxamine (1 microM), indicating that it was a beta 1-adrenoceptor-mediated action. The positive chronotropic effect of higenamine was not changed by pretreatment with reserpine (4 mg/kg, i.p., 4 hr). Aconitine (0.16-0.25 microM) induced tachyarrhythmia in right atria was attenuated by quinidine (1 microM), atropine (8.6 microM) and AF-DX 116 (8.6 microM), suggesting that aconitine activates sodium channels and muscarinic receptors. Higenamine (2.5 nM) and dobutamine (1 nM) did not cause chronotropic effects by themselves, but enhanced the aconitine-induced tachyarrhythmia. These results indicate that higenamine is a beta 1-adrenoceptor full agonist in murine atria and that the aconitine-induced tachyarrhythmia is augmented by the beta 1-adrenergic action of higenamine.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Makino
M
M
Takamura
Y
Y
Islam
M A
MA
Kimura
M
M
D000157:Aconitine / Q000037:antagonists & inhibitors; D058671:Adrenergic beta-1 Receptor Antagonists; D000470:Alkaloids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced* / Q000503:physiopathology; D044005:Tetrahydroisoquinolines
D058671:Adrenergic beta-1 Receptor Antagonists; D000470:Alkaloids; D002316:Cardiotonic Agents; D018727:Muscarinic Antagonists; D044005:Tetrahydroisoquinolines; C012348:higenamine; D000157:Aconitine