Chronotropic and inotropic effects of 3 kinds of alpha-adrenergic blockers on the isolated dog atria.

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Abstract
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 [2-[4-(n-butyryl)-homopiperazine-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride, were compared. When phenoxybenzamine was administered into the cannulated sinus node artery, positive chronotropic and inotropic responses were induced in doses of 10-300 .mu.g. Phentolamine also produced positive responses, but at larger doses such as 100 and 300 .mu.g, 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. Negative responses to E-643 and phentolamine were not modified by atropine treatment. Sinus tachycardia induced by .alpha.-blockers in situ may be due to 3 different mechanisms, i.e., reflex tachycardia induced by the hypotension, augmented catecholamine release mediated by the block of the presynaptic .alpha.-adrenoceptors, and direct catecholamine release from locally innervated sympathetic nerve terminals.

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