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 propranolol daily for 7 days, to determine whether changes in beta-adrenergic 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 the 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 stimulation with phenylephrine did not differ between age groups, either before or after propranolol withdrawal. By contrast, pressor and bradycardic responses produced by combined alpha- and beta-adrenergic stimulation with epinephrine after propranolol withdrawal, though unaltered in 3-month-old rats, were enhanced in 12-month-old rats. Hence after sudden propranolol withdrawal beta-adrenergic sensitivity in conscious rats was gradually restored, rather than being enhanced, but more slowly at 12 than at 3 months of age. These results suggest that following abrupt cessation of prolonged propranolol treatment, restoration of normal beta-adrenergic sensitivity becomes delayed in older rats.