IMPAIRED EXPRESSION OF G(S-ALPHA) PROTEIN MESSENGER-RNA IN RAT VENTRICULAR MYOCARDIUM WITH AGING

We have recently reported that the responsiveness of adrenoceptors is decreased with aging in rat ventricular myocardium. Thus, the current study determined aging-dependent changes in: (a) characteristics of myocardial G proteins as determined by Western blot analysis; (b) steady-state levels of G protein mRNA as determined by Northern blot analysis; and (c) the inotropic response to isoproterenol, a beta-adrenoceptor agonist. Cardiac preparations were isolated from male Wistar rats of 6 (adult) and 24 (old) months old. Compared with adults, aging decreased the combined level of the three G(s alpha) subunits (45, 47 and 52 kDa) by a total of 23% in ventricular membrane preparations. In contrast, levels of G(i alpha) (40/41 kDa), G(q alpha) (42 kDa), G(o alpha) (39 kDa) and G(common beta) (35/36 kDa) immunoreactivity were not affected by aging in the same membrane preparations. In ventricular myocardium, steady-state levels of G(s alpha) mRNA(1.9 kb) decreased by 20-28% between 6 and 24 months of age with no change in G(i alpha) mRNA (2.4 kb). An aging-associated decline in beta-adrenergic stimulation was observed in the maximum positive inotropic effect elicited by isoproterenol in the presence of prazosin in left papillary muscles, with no change in ED(50) values. These results suggest that age-related changes in cardiac excitation and contraction coupling following beta-adrenoceptor stimulation are mediated, at least in part, by G(s alpha) protein dysfunction.