PHARMACOLOGIC ANALYSIS OF CHRONOTROPIC AND INOTROPIC RESPONSES TO 5-HYDROXYTRYPTAMINE IN THE DOG HEART

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Abstract
Inotropic and chronotropic effects of 5-hydroxytryptamine (5-HT) were investigated in 25 isolated canine atrial preparations and 3 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 1-300 .mu.g. In small doses of 1-3 .mu.g, 5-HT induced a negative chronotropic and inotropic response. At relatively higher doses over 10 .mu.g, 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 desipramine, 5-HT-induced negative responses were potentiated. 5-HT-induced negative chronotropic and inotropic responses were not inhibited by methylsergide and atropine. 5-HT apparently induces a direct negative chronotropic and inotropic response and an indirect positive response via its tyramine-like action.