Abstract
Inotropic and chronotropic effects of 5-hydroxytryptamine (5-HT) were investigated in twenty-five isolated canine atrial preparations and three isolated paced ventricular preparations which were suspended in the bath and perfused with arterial blood from the carotid artery of the heparinized support dog. 5-HT was administered into the cannulated sinus node artery in a dose range of I to 300 μg. In small doses of 1 to 3 μg, 5-HT induced a negative chronotropic and inotropic response. At relatively higher doses over 10 μg, 5-HT induced a biphasic response: a slight negative chronotropic and inotropic response, followed by a long-lasting positive response. With large doses, only a positive chronotropic and inotropic response was induced in the majority of cases. Even in the ventricular preparations, 5-HT produced a similar response pattern in inotropism. 5-HT-induced positive chronotropic and inotropic responses were completely inhibited by pretreatment with an adrenergic beta-blocking agent, propranolol, or a non-depressant beta-blocking agent, carteolol, and desipramine, but were not influenced by tetrodotoxin treatment. After the treatment with carteolol or despramine, 5-HT-induced negative responses were potentiated. 5-HT-induced negative chronotropic and inotropic responses were not inhibited by methysergide and atropine. From these results, it is suggested that 5-HT induces a direct negative chronotropic and inotropic response and an indirect positive response via its tyramine-like action.
