EFFECT OF AGING AND PROPRANOLOL ADMINISTRATION ON MYOCARDIAL BETA-ADRENOCEPTOR RECEPTOR FUNCTION IN MATURE RATS

Ageing is accompanied by diminishing myocardial tissue beta-adrenocept or responses. The relative contribution of maturation and senescence t o reported age-related changes in cell-surface beta-adrenoceptor dysfu nction has not been established, since previous investigation has inco rporated young rats lacking full maturity. We have examined myocardial ventricle membrane beta-adrenoceptor function in mature young (6 mont h) and old (26 month) male Wistar rats and the effect of propranolol i nfusion for seven days on beta-adrenoceptor function in these groups. beta(1)-adrenoceptors comprised 63-72% of total beta-adrenoceptor dens ity in both groups. beta(1)-adrenoceptor densities were similar in you ng and old rats (young, 20.4 +/- 2.3; old, 24.7 +/- 1.4 fmol/mg protei n +/- 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 da ys with miniosmotic pumps was accompanied by an increase in beta(1)- a nd beta(2)-adrenoceptor densities in young rats only (beta(1)-, 38%, P < 0.05; beta(2)- 52%, P < 0.025). beta(1)-adrenoceptor agonist affini ty and adenylate cyclase response to isoprenaline, GTP, Gpp(NH)p, Mn2 and forskolin were not affected by age or propranolol infusion in eit her age-group. These findings demonstrate that male Wistar rats do not exhibit changes in myocardial ventricle beta-adrenoceptor-G-protein c oupling capacity or adenylate cyclade activation with ageing beyond ma turity. There is, however, an age-related impairment of beta-adrenocep tor upregulation in response to propranolol that could reflect age-rel ated deceleration of mechanisms of G-protein-coupled receptor upregula tion.