title: The effects of nadolol on various cardiac tissues in normoxia, and on atrial muscle in simulated ischaemia.
abstract: Nadolol, a non-selective beta-blocker with a long duration of action, reportedly is devoid of membrane stabilizing action. Since such action is augmented by ischaemic conditions, it was of interest to investigate whether, in simulated ischaemia, a direct membrane effect of nadolol might be revealed. We have confirmed that in normoxia nadolol had no effects on intracellulary recorded potentials in isolated rabbit atrial or ventricular muscle at a concentration of 4.84 microM, but significantly reduced action potential amplitude and maximum rate of depolarisation at 14.5 microM. In Purkinje cells a small reduction of action potential amplitude was produced by 1.61 microM nadolol, but the effect was not increased by nadolol 4.84 microM. There were no drug-induced changes in action potential duration (APD), spontaneous frequency, conduction velocity, contractions, electrical threshold, effective refractory period or the maximum frequency at which a stimulus could be followed. Nadolol 14.5 microM did not reduce the positive inotropic effect of increasing extracellular calcium concentrations. Nadolol was 25 times less potent than procaine as a local anaesthetic on desheathed frog nerve. In a solution simulating ischaemia (8 mM KCl, 10 mM NaHCO3, gassed with 20% O2, pH 7.0) nadolol had a significant class 1 action on atrial muscle, however, even at 4.84 microM and reduced the shortening of APD caused by the solution. It is concluded that nadolol has no class 1, 3 or 4 antiarrhythmic activity in normoxia, but could have an additional protective effect in ischaemic myocardium against the arrhythmogenic factor of shortened APD.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009248:Nadolol; D011412:Propanolamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D011898:Ranidae
chemical_list: D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D011412:Propanolamines; D009248:Nadolol