Interactions of Sympathomimetic Drugs, Propranolol and Phentolamine, on Atrial Refractory Period and Contractility

Abstract

Govier, Mosal, Whittington & Broom (1966) reported that 5 /AM of adrenaline increases atrial refractory period. As in the presence of the a-receptor antagonist phenoxybenzamine adrenaline reduced atrial refractory period, the authors concluded that the increase in atrial refractory period is an action on a-receptors. Shortening of atrial refractory period by adrenaline was assumed to be an effect on fl-receptors, as the fl-receptor antagonist pronethalol inhibited it.As we had found that a-receptor antagonists such as phenoxybenzamine and phentolamine can potentiate the effect of noradrenaline on atrial contractility (Benfey & Greeff, 1961), we wondered whether the effect of phenoxybenzamine observed by Govier et a1. (1966) was due to a potentiation of adrenaline effects, as large concentrations of adrenaline shorten refractory period. Therefore we decided to study a wide range of concentrations of various sympathomimetic drugs.We found that isoprenaline shortens refractory period in all concentrations used and that phenylephrine prolongs it. Adrenaline had a biphasic action: it prolonged refractory period in small and shortened it in large concentrations. Noradrenaline was similar to adrenaline but less potent in prolonging the refractory period. A small concentration of phentolamine inhibited prolongation of refractory period by adrenaline, noradrenaline and phenlyephrine without increasing the effect of these drugs on contractility. In contrast, cocaine potentiated effects of noradrenaline and adrenaline on atrial contractility without inhibiting prolongation of refractory period by adrenaline. It thus appears that the prolongation of atrial refractory period by phenylephrine and small concentrations of adrenaline and noradrenaline is an effect on a-receptors.It was observed incidentally that concentrations of the fl-receptor antagonist propranolol, which were quite effective against isoprenaline, had little or no effect on the actions of adrenaline, noradrenaline and phenylephrine on atrial contractility, although these concentrations of propranolol had effects on the f8-receptors responsible for shortening of the refractory period.x

Lack of relationship between myocardial cyclic AMP concentrations and inotropic effects of sympathomimetic amines

“…The inotropic effect of phenylephrine on the rabbit atrium was not altered by pretreatment with reserpine (Lee & Yoo, 1964). Studies with a-adrenoceptor blocking drugs gave evidence that phenylephrine acts on a-adrenoceptors in the isolated rat ventricle (Wenzel & Su, 1966) and rabbit left atrium (Benfey & Varma, 1967). ,3-Adrenoceptor blocking drugs inhibited the inotropic effect of phenylephrine on the rabbit right atrium (Lee & Yoo, 1964;Leong & Benfey, 1968) and on the isolated perfused dog heart (Kabela et d., 1969).…”

Transformation of Adrenergic Receptors in the Myocardium

“…The demonstration of a minor a-adrenergic component in the effect of catecholamines on mammalian hearts (Wenzel and Su, 1966;Gov;er et !l., 1966;Benfey and Varma, 1967;Govier, 1968) suggested that sorne similar receptor transformation might also be possible in the mammalian myocardium.…”

Effect of Hypothyroid Status on Myocardial Responses to Sympathomimetic Drugs

“…Recently, it was tried to explore some effects of thyroidectomy on the response of alpha and beta adrenergic receptor mechanisms to catecholamines (6). A few workers have reported the existence of both alpha and beta receptors in the hearts of mammals (7,8).<BR> Present studies reported here were made in an attempt to clarify some of the discrepancies in many reports by seeking a quantitative difference between different types of cardiac adrenergic receptor mechanisms after 6-propyl-2-thiouracil (PTU) treatment.…”