Ex vivo examination of beta-adrenoceptor characteristics after propranolol withdrawal

Propranolol (3.6 mg kg-1 day-1) was administered to guinea pigs for 14 days via subcutaneously implanted "Alzet" osmotic minipumps. Blockade of cardiac and vascular beta-adrenoceptors was confirmed by a depression of heart rate and blood pressure responses to isoprenaline in anaesthetized animals. After 14 days of propranolol treatment, minipumps were removed and 48 h later beta-adrenoceptor sensitivity was determined in cardiac and lung tissues. Left atrial inotropic responses were unaltered following propranolol withdrawal. However, right atrial chronotropic responses to sympathomimetic amines were supersensitive when compared with tissues from animals implanted with empty minipumps. Relaxation responses of lung strip preparations to beta-adrenoceptor agonists after withdrawal of propranolol were similar to controls. (3H)Dihydroalprenolol binding to ventricular and lung tissue indicated that there was no change in either the dissociation constant (KD) or the maximum number of (3H)DHA binding sites (Bm) in these tissues. These results suggest that following withdrawal from beta-adrenoceptor antagonist treatment there is a selective increase in the chronotropic sensitivity of the heart to sympathomimetic amines.