PROPRANOLOL AND ISOPROTERENOL IN DOGS DEPRIVED OF SYMPATHETIC NERVE ACTIVITY

¹ Anaesthesia Laboratory of the Harvard Medical School at the Massachusetts General Hospital, Boston, Massachusetts

The direct effects of propranolol and its interaction with isoproterenol on heart rate, myocardial contractile force, arterial pressure, aortic flow and atrial pressures were studied in anesthetized dogs in which autonomic tone had been eliminated by sympathetic (epidural) and parasympathetic (atropine) block. Propranolol in doses from 0.01 to 1 mg/kg caused no significant changes in any of these cardiovascular parameters. A dose of 3 mg/kg of propranolol did cause a small decrease in heart rate, contractile force and blood pressure, and increased left atrial pressure. The beta-adrenergic effects of 2 µg/kg of isoproterenol were blocked progressively by increasing amounts of propranolol, and were eliminated completely by the 3-mg/kg dose. After 3 mg/kg of propranolol, higher doses of isoproterenol surmounted the effects of the beta-receptor block on heart rate, contractile force and atrial pressure. In addition, high doses of isoproterenol after beta-receptor blockade caused a marked rise in mean arterial pressure and in calculated peripheral resistance. These peripheral effects of isoproterenol were not seen in dogs which had received 10 mg/kg of phenoxybenzamine in addition to the propranolol. The results show that, when endogenous neurogenic tone is eliminated, propranolol has no direct depressant effect upon cardiovascular function in doses which cause powerful beta-receptor blockade. In addition it is shown that isoproterenol has a marked, but not very potent, alpha-adrenergic action, which becomes evident after blockade of its beta-adrenergic effects, and which can in turn be eliminated by the use of an alpha-receptor blocking agent.