Positive and negative chronotropic response of the S-A node to oxyfedrine

Direct perfusion of the sinus node artery under a constant pressure of 100 mmHg was carried out in vagotomized dogs. "Selective" injection of L-3-methoxy-omega-(1-hydroxy-1-phenylisopropylamino) propiophenone hydrochloride (oxyfedrine) into the sinus node artery induced three types of chronotropic response; a pronounced sinus tachycardia, an initial bradycardia followed by sustained tachycarcia, or a definite sinus bradcardia alone. The paradoxical sinus bradycardia induced by oxyfedrine was more pronounced at higher doses of the compound, whereas it was nver produced by the injection of isoproterenol. The oxyfedrine-induced sinus tachycardia, which occurred even in reserpinized preparations, was not suppressed by the treatment with tetrodotoxin, hexamethonium or bretylium, but it was selectively inhibited by propranolol. Atropine, tetrodotoxin or hexamethonium did not prevent the occurrence of sinus bradycardia induced by oxyfedrine, and physostigmine failed to enhance the response. The present study indicates that the oxyfedrine-induced tachycardia is mediated mainly by a direct stimulating action on adrenergic beta-receptors, while the bradycardia appears to be induced by a direct depressant action on the S-A node.