MECHANISMS OF AGING--ENHANCED HEART ADENOSINE

衰老的心脏对β-肾上腺素能刺激的反应减弱 与年轻的成人心脏相比。这个实验室的研究表明 衰老的心脏产生更多的腺苷和更大的间质 腺苷水平。这被认为可以促进增强的抗肾上腺素能 腺苷的作用，进而降低老年人的反应性 心脏对β-肾上腺素能的刺激。建议的目的是 该项目是为了确定为什么老年人的心脏会产生更多的腺苷 并且具有较高的核苷的间隙水平。灌流大鼠 心脏也将被用来研究代谢机制。 是衰老导致腺苷产量增加的原因 心肌。衰老对腺苷摄取和代谢的影响 使用灌流的心脏进行研究。腺苷释放的影响， 将利用心室肌细胞进一步研究摄取和代谢。 和老年心脏的内皮细胞来描绘衰老是如何影响的 这些过程。这个项目代表了一个相对较新的概念 涉及腺苷，这可能是解释减少的重要原因 哺乳动物心脏的β-肾上腺素能反应性 衰老。

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.