MECHANISMS OF AGING--ENHANCED HEART ADENOSINE

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Aged hearts have a reduced response to beta-adrenergic stimulation compared to young adult hearts. Studies from this laboratory indicate that aged hearts produce more adenosine and have a greater interstitial level of adenosine. This is thought to foster an enhanced antiadrenergic action of adenosine and, in turn, reduce the responsiveness of aged adult hearts to beta-adrenergic stimulation. The purpose of the proposed project is to determine why the aged adult heart produces more adenosine and has a higher interstitial level of the nucleoside. Perfused rat heart will also be used to investigate the metabolic mechanisms responsible for the increased production of adenosine by the aging myocardium. The effect of aging on adenosine uptake and metabolism will be investigated using perfused hearts. The effect of adenosine release, uptake and metabolism will be further studied using ventricular myocytes and endothelial cells from aged hearts to delineate how aging affects these processes. This project represents a relatively new concept involving adenosine that may be important in explaining the decrement of beta-adrenergic responsiveness of the mammalian heart observed with aging.