AGE-RELATED DECLINE IN BETA-ADRENERGIC AND ADENOSINE A(1) RECEPTOR FUNCTION IN THE HEART ARE ATTENUATED BY DIETARY RESTRICTION

Previously published reports from this laboratory have shown that the antiadrenergic effect of adenosine A, agonists declines with age in th e rat heart [Gao et al. (1997) J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a decrease in coupling between adenosin e A(1) receptors (AdoA(1)R) and guanine nucleotide-binding proteins [C ai et al. (1997) Circ Res 81:1065-1071]. Dietary restriction (DR; 60% calories of ad libitum) has been shown to attenuate age-related change s in cellular signal transduction pathways. Therefore, the present stu dy investigated whether DR altered the age-related changes in AdoA(1)R -mediated function in senescent rat hearts. Ventricular membranes were isolated from the hearts of ad libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In AL rats, there was an age-re lated decline in isoproterenol (ISO)-stimulated adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO-stimulated cycl ase was attenuated in DR animals. In AL rats, inhibition of ISO-stimul ated adenylyl cyclase by the AdoA(1) R agonist, N-6-p-sulfophenyladeno sine (SPA) decreased with age. In DR rats, the age-related decline in inhibition was attenuated. Previous results from this laboratory indic ated that in AL fed rats, there was an age-related decrease in the per centage of high-affinity binding sites for SPA, from 55% at 6 months t o 23% at 24 months. Diet restriction attenuated this age-related shift in high-affinity binding sites so that the percentage of high-affinit y sites at 24 months was 42%. Our results suggest that DR maintains Ad oA(1)R function by preventing a loss of high-affinity AdoA(1)R sites.