Beta-adrenoceptor blockade and atrio-ventricular conduction in dogs. Role of intrinsic sympathomimetic activity.
1 Atrio-ventricular conduction and its modifications induced by six beta-adrenoceptor blocking agents and isoprenaline have been investigated in the anaesthetized dog using the extrastimulus technique and measuring atrial (AERP), nodal (NERP), global (GERP) effective refractory periods as well as global functional refractory period (GFRP). 2 When beta-adrenoceptor blockade was produced by (+/-)-propranolol (beta 1 + beta 2-adrenoceptor blockade) which is devoid of intrinsic sympathomimetic activity (ISA) but has membrane stabilizing effects (MSE), sotalol (beta 1 + beta 2-adrenoceptor blockade, no ISA, no MSE) and atenolol (beta 1-adrenoceptor blockade, no ISA, no MSE), all parameters were significantly increased. When beta-adrenoceptor blockade was achieved with pindolol (beta 1 + beta 2-adrenoceptor blockade) and practolol (beta 1-adrenoceptor blockade) which have ISA but no MSE, all parameters remained unchanged, as was also the case with (+)-propranolol, which has MSE but neither ISA nor beta-adrenolytic properties. 3 Isoprenaline at high doses significantly reduced the refractory periods but when infusion was stopped, marked but reversible conduction depression was observed. 4 It thus appears that beta-adrenoceptor blockade but not MSE is responsible for the onset of atrial and AV-conduction impairment and that ISA affords protection against this impairment.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D013566:Sympathomimetics
D000319:Adrenergic beta-Antagonists; D013566:Sympathomimetics; D011433:Propranolol; D007545:Isoproterenol