Chronotropic and inotropic effects of 3 kinds of alpha-adrenergic blockers on the isolated dog atria.
Using the isolated and blood-perfused dog atrial preparation, chronotropic and inotropic responses to 3 kinds of alpha-adrenergic blockers, phentolamine, phenoxybenzamine, and E-643, were compared. When phenoxybenzamine was administered into the cannulated sinus node artery, positive chronotropic and inotropic responses were induced in doses of 10-300 microgram. Phentolamine also produced positive responses, but at larger doses such as 100 and 300 microgram, accompanying initial negative responses. E-643 usually produced only negative chronotropic and inotropic effects. Positive responses to phenoxybenzamine and phentolamine were significantly suppressed by propranolol, and negative responses to E-643 and phentolamine were not modified by atropine treatment. From these results and previous reports, it is assumed that sinus tachycardia induced by alpha-blockers in situ may be due to 3 different mechanisms, i.e., 1) reflex tachycardia induced by the hypotension, 2) augmented catecholamine release mediated by the block of the presynaptic alpha-adrenoceptors, and 3) direct catecholamine release from locally innervated sympathetic nerve terminals.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D010643:Phenoxybenzamine; D001285:Atropine; C018176:bunazosin; D011433:Propranolol; D010646:Phentolamine