Direct and beta adrenergic blocking actions of nadolol (SQ 11725) on electrophysiologic properties of isolated canine myocardium

J. K. Gibson, H. Gelband, A. L. Bassett

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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. The authors 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.

Original languageEnglish (US)
Pages (from-to)702-710
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume202
Issue number3
StatePublished - Dec 1 1977

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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