ANTAGONISM BY PROPRANOLOL OF THE CARDIAC CHRONOTROPIC RESPONSE TO NOREPINEPHRINE OR TO TRANSMURAL ELECTRICAL STIMULATION

¹ Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington

Earlier studies attest to the fact that electrical stimulation of intranodal nerve fibers of the rabbit isolated atrial preparation causes the release of autonomic mediators. Such a preparation was used to compare the adrenergic blockade by propranolol of the chronotropic response to direct electrical stimulation with that in response to applied norepinephrine. Three concentrations of propranolol were studied, 10^-9, 10^-8 and 10^-7 g/ml. In preparations treated with atropine, propranolol antagonized the positive chronotropic action produced by either applied or endogenously released amine. Maximal blockade of the positive chronotropic response induced by electrical stimulation was achieved within 20 min by a concentration of 10^-7 g/ml of propranolol. The maximal chronotropic response to electrical stimulation was significantly depressed by propranolol as a function of concentration. The positive chronotropic response to tyramine was blocked by propranolol; that is, concentration-response curves were displaced downward and to the right. In contrast, concentration-response curves for norepinephrine were shifted to the right. Although the displacement of the concentration-response curves and the frequency-response curves suggests a difference in the mechanism of blockade by propranolol in the two cases, it is postulated that in both cases the blockade is the result of surmountable inhibition.