In 1958, Powell and Slater (1) first described that DCI had beta-adrenergic blocking activity even though it included beta-adrenergic stimulations. Such property was found also in methoxamine besides its alpha-adrenergic stimulant activity (2, 3). In the follow ing decade, many beta-adrenergic blocking agents have been synthesized successively (4-8) and one of them, propranolol was first introduced in the clinical medicine. Since Ahlquist classified alpha and beta-adrenergic receptors, it has been well established that positive chronotropic and inotropic effects and vaso and broncho-dilator actions of cate cholamines are mediated through an interaction between drug and beta-receptor. How ever, it is not gotten clear, whether all beta-adrenergic blocking agents would have the same potency to block beta-adrenergic receptor in different organs.In many experiments, the blockade of the positive chronotropic response to cate cholamines has been chosen in order to evaluate the potency of beta-adrenergic blocking agents. Excised preparation of atria (3, 9) and also whole animals (5, 7) were used, while drug was added in the bath or given intravenously. James and Nadeau (10) examined the effect of DCI on the sinoatrial pacemaker activity when it was given selectively into the sinus node artery. In this paper we compared the effect of beta-adrenergic blocking activity of DCI (1), methoxamine (2), propranolol (4), MJ 1999 (5), H 56/28 (6), LB 46 (7) and I.C.I. 50 172 (8) selectively administered into the sinus node artery, while isopre naline was used as an agonist.
METHODSThirty-seven mongrel dogs, of both sexes, weighing 11 to 18 kg were used. Animals were anesthetized with sodium pentobarbital, 30 mg/kg, intravenously. A tracheal tube was inserted and the artificial respiration was performed by a Bird respirator "mark 8" with room air. The heart was usually exposed through an intercostal incision at the right fourth intercostal space. The pericardium was opened and the heart was kept its original position by making a pericardial cardle. Both vagus nerves were cut at the mid