AGE-RELATED DELAY IN RECOVERY OF BETA-ADRENERGIC SENSITIVITY AFTER ABRUPT PROPRANOLOL WITHDRAWAL IN RATS

We compared cardiovascular responses to various adrenergic agonists in conscious 3-month and 12-month old rats that had been treated with pr opranolol daily for 7 days, to determine whether changes in beta-adren ergic hypersensitivity induced by abrupt propranolol withdrawal would differ with age. Depressor and tachycardic responses elicited by beta- adrenergic stimulation with isoproterenol were still reduced during th e first 3 days following propranolol withdrawal, but were restored to pretreatment levels, more slowly in 12-month than in 3-month-old rats. Opposite pressor and bradycardic responses to alpha-adrenergic stimul ation with phenylephrine did not differ between age groups, either bef ore or after propranolol withdrawal. By contrast, pressor and bradycar dic responses produced by combined alpha- and beta-adrenergic stimulat ion with epinephrine after propranolol withdrawal, though unaltered in 3-month-old rats, were enhanced in 12-month-old rats. Hence after sud den propranolol withdrawal beta-adrenergic sensitivity in conscious ra ts was gradually restored, rather than being enhanced, but more slowly at 12 than at 3 months of age. These results suggest that following a brupt cessation of prolonged propranolol treatment, restoration of nor mal beta-adrenergic sensitivity becomes delayed in older rats.