Direct and beta adrenergic blocking actions of nadolol (SQ 11725) on electrophysiologic properties of isolated canine myocardium.
Effects of nadolol, a new beta adrenergic antagonist, were determined on transmembrane potentials of canine Purkinje fibers and ventricular and atrial muscle. Significant alterations in Purkinje fiber potentials occurred only with nadolol concentrations of 10(-4) M or greater. After 1 hour exposure to 10(-4) M, resting potential and action potential amplitude were reduced; at 3 hours, action potential rate of rise, phase 2 duration and action potential duration at 75% repolarization also were decreased. 10(-3) M nadolol also was depressant and, additionally, consistently reduced membrane responsiveness. Nadolol (10(-8)-10(-4) M) had no significant effects on effective refractory period. Ventricular and atrial muscle were less sensitive to all drug concentrations. Nadolol (10(-8)-10(-4) M) had little action on automaticity in normal, ouabain-treated or stretched Purkinje fibers but markedly decreased catecholamine-enhanced automaticity. In isoproterenol-treated Purkinje fibers, pA2 for nadolol was 8.2 and 7.7 for propranolol. Nadolol (10(-3) M or less) did not affect isometric force developed by isolated canine atrial trabeculae. We suggest that direct membrane depressant effects of nadolol do not contribute to its antiarrhythmic activity and that its beta adrenergic blocking ability is beneficial in catecholamine-related cardiac ectopia.
Direct and beta adrenergic blocking actions of nadolol (SQ 11725) on electrophysiologic properties of isolated canine myocardium. Effects of nadolol, a new beta adrenergic antagonist, were determined on transmembrane potentials of canine Purkinje fibers and ventricular and atrial muscle. Significant alterations in Purkinje fiber potentials occurred only with nadolol concentrations of 10(-4) M or greater. After 1 hour exposure to 10(-4) M, resting potential and action potential amplitude were reduced; at 3 hours, action potential rate of rise, phase 2 duration and action potential duration at 75% repolarization also were decreased. 10(-3) M nadolol also was depressant and, additionally, consistently reduced membrane responsiveness. Nadolol (10(-8)-10(-4) M) had no significant effects on effective refractory period. Ventricular and atrial muscle were less sensitive to all drug concentrations. Nadolol (10(-8)-10(-4) M) had little action on automaticity in normal, ouabain-treated or stretched Purkinje fibers but markedly decreased catecholamine-enhanced automaticity. In isoproterenol-treated Purkinje fibers, pA2 for nadolol was 8.2 and 7.7 for propranolol. Nadolol (10(-3) M or less) did not affect isometric force developed by isolated canine atrial trabeculae. We suggest that direct membrane depressant effects of nadolol do not contribute to its antiarrhythmic activity and that its beta adrenergic blocking ability is beneficial in catecholamine-related cardiac ectopia.