Competitive Antagonism Between Isoproterenol and a New Beta-Receptor Adrenergic Blocking Agent, Propranolol.

Abstract

Summary The effects of graded doses of isoproterenol on mean systemic arterial pressure and myocardial contractile force were studied in anesthetized dogs before and after administration of graded doses of a new beta-receptor blocking agent, propranolol. It was found that, with geometrically increasing doses of propranolol, the effects of given doses of isoproterenol on systemic arterial pressure and myocardial contractile force decreased progressively. However, the larger doses of isoproterenol surmounted the blocking effect of propranolol on myocardial contractile force. Dose-response curves of isoproterenol after graded doses of propranolol indicate the existence of competitive antagonism between isoproterenol and propranolol. In addition, after administration of propranolol, the effect of isoproterenol on systemic arterial pressure was found to become biphasic, an initial increase being followed by a decrease. Hence, it is postulated that isoprotenerol possesses a vasoconstrictor (alpha-receptor stimulator) property which is usually hidden by a more marked vasodilator (beta-receptor stimulator) property of the drug.