Pharmacological analysis of beta adrenoceptor blockade-induced coronary blood flow redistribution in dogs using l-penbutolol.
The effects of l- and d-penbutolol on regional myocardial blood flow (assessed by means of tracer microspheres) and on ST-segment elevation in ischemic and nonischemic areas of the canine left ventricle have been investigated under different experimental conditions. l-Penbutolol reduced transmural coronary blood flow and induced its redistribution from the epicardium to the endocardium in both ischemic and nonischemic areas. This favorable effect was abolished under atrial pacing or after bilateral stellectomy or in the presence of phenoxybenzamine. d-Penbutolol did not induce coronary blood flow redistribution. These results indicate that the redistribution phenomenon occurs only if both a beta adrenoceptor blockade-induced bradycardia and a beta adrenoceptor blockade-induced reinforcement of alpha adrenoceptors-mediated coronary vasoconstrictor tone are simultaneously achieved l-Penbutolol alone or in the presence of phenoxybenzamine decreased ST-segment elevation in ischemic areas, but this effect was abolished by atrial pacing, confirming the major role of bradycardia in the reduction of ischemic injury.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010394:Penbutolol / Q000494:pharmacology; D013237:Stereoisomerism; D014655:Vascular Resistance / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010394:Penbutolol