Effect of ageing and propranolol administration on myocardial beta-adrenoceptor receptor function in mature rats.
Ageing is accompanied by diminishing myocardial tissue beta-adrenoceptor responses. The relative contribution of maturation and senescence to reported age-related changes in cell-surface beta-adrenoceptor dysfunction has not been established, since previous investigation has incorporated young rats lacking full maturity. We have examined myocardial ventricle membrane beta-adrenoceptor function in mature young (6 month) and old (26 month) male Wistar rats and the effect of propranolol infusion for seven days on beta-adrenoceptor function in these groups. beta 1-adrenoceptors comprised 63-72% of total beta-adrenoceptor density in both groups. beta 1-adrenoceptor densities were similar in young and old rats (young, 20.4 +/- 2.3; old, 24.7 +/- 1.4 fmol/mg protein +/- S.E.). beta 2-adrenoceptor densities were higher in older rats (young, 8.2 +/- 0.5, n = 9; old, 13.6 +/- 1.8, n = 9 fmol/mg protein +/- S.E., P < 0.025). Subcutaneous infusion of propranolol for seven days with miniosmotic pumps was accompanied by an increase in beta 1- and beta 2-adrenoceptor densities in young rats only (beta 1-, 38%, P < 0.05; beta 2- 52%, P < 0.025). beta 1-adrenoceptor agonist affinity and adenylate cyclase response to isoprenaline, GTP, Gpp(NH)p, Mn2+ and forskolin were not affected by age or propranolol infusion in either age-group. These findings demonstrate that male Wistar rats do not exhibit changes in myocardial ventricle beta-adrenoceptor-G-protein coupling capacity or adenylate cyclade activation with ageing beyond maturity.(ABSTRACT TRUNCATED AT 250 WORDS)
Conlon
D
D
Department of Clinical Pharmacology, Royal College of Surgeons In Ireland, Dublin.
Johnston
A
A
O'Malley
K
K
Turner
P
P
Kilfeather
S
S
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol