Beta-adrenoceptor blocking effects of a selective beta 2-agonist, mabuterol, on the isolated, blood-perfused right atrium of the dog.

1. Effects of (+/-)-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.- butylamino-ethanol hydrochloride (mabuterol) on pacemaker activity and atrial contractility were investigated in the isolated and blood-perfused right atrium of the dog. 2. Mabuterol, injected into the sinus node artery of the isolated atrium, dose-dependently increased atrial rate and contractile force at doses of 0.01-10 nmol but the responses to over 10 nmol of mabuterol gradually decreased and mabuterol at higher doses induced biphasic cardiac responses, i.e., negative followed by positive cardiac responses. 3. The maximal increases in atrial rate and contractile force induced by mabuterol were 41.4% and 12.9%, respectively, of the maximal chronotropic and inotropic effects of isoprenaline. 4. Positive chronotropic and inotropic responses to mabuterol were dose-dependently inhibited by a selective beta 2-adrenoceptor antagonist, ICI 118,551. These responses were only slightly attenuated by atenolol. 5. Mabuterol (1-300 nmol) dose-dependently inhibited both dobutamine- and procaterol-induced positive chronotropic and inotropic responses. 6. These results indicate that mabuterol causes weak positive chronotropic and inotropic effects on the perfused canine right atrium by activating beta 2-adrenoceptors, and that higher concentrations non-selectively block both beta 1-and beta 2-adrenoceptors.