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.
Teräväinen
T L
TL
Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City 66103.
Buñag
R D
RD
D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004351:Drug Resistance / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D011433:Propranolol; D004837:Epinephrine