COMBINATIONS OF ALPHA AND BETA ADRENERGIC BLOCKERS IN ISOLATED GUINEA-PIG ATRIA

¹ College of Pharmacy, The Ohio State University, Columbus, Ohio

The ability of alpha blockers to influence the effectiveness of beta blockade was studied in the isolated guinea-pig atrium. Chronotropic effect was used as the test parameter. Cumulative dose- response curves for the relatively specific beta adrenergic agonist, isoproterenol, were determined in control atria, and for isoproterenol in the presence of 1) phentolamine ( 10^-6 M), 2) beta antagonists, (±)-propranolol (3 x 10^-7 M), (±)-sotalol (10^-6 M), (±)-methoxamine (3 x 10^-5 M) and (-)-N-isopropyl-p-nitrophenylethanolamine (10^-6 M), and 3) in the presence of phentolamine plus each of the above beta antagonists. The influence of phentolamine on beta adrenergic blockade was determined by comparing dose ratios for beta blockers in the presence and absence of phentolamine. In no case was there antagonism between phentolamine and beta blockers; however, there was a slight tendency for the effects to be additive. Similar results were obtained when Dibenamine (10^-5 M) was substituted for phentolamine.