Ex Vivo Examination of β-Adrenoceptor Characteristics After Propranolol Withdrawal

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Abstract
Propranolol (3.6 mg/kg per day) was administered to guinea pigs for 14 days via s.c. 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 anesthetized 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. 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 Kd or the maximum number of (3H)DHA binding sites (Bm) in these tissues. Following withdrawal from .beta.-adrenoceptor antagonist treatment there apparently is a selective increase in the chronotropic sensitivity of the heart to sympathomimetic amines.