ADENOSINE AND BETA-ADRENERGIC ACTION IN THE AGING HEART

老年心脏对β-肾上腺素能刺激的反应减弱，因为 与年轻的成年人的心脏相比。初步研究表明， 老年人的心脏比年轻人的心脏产生更多的腺苷。 根据我们以前的工作，众所周知，腺苷有一个 心脏中的抗肾上腺素能作用。建议的总体目的是 该项目旨在研究腺苷在脑血管紧张素转换酶反应性降低中的作用。 老年成人心脏对β-肾上腺素能的刺激。 来自逐渐老化的成年大鼠的心脏将被灌流以研究 衰老、腺苷生成与衰老的关系 β-肾上腺素能收缩(压力发展的程度和速度)和 代谢(环磷酸腺苷、环磷酸腺苷依赖的蛋白激酶、蛋白质 磷酸化，糖原磷酸酶)变量。腺苷的作用 老年成人心脏对β-肾上腺素能反应减弱 刺激将通过以下方式进行探索：1)确定 老化的心脏到腺苷，2)减少腺苷在心脏中的积聚 老化心脏的血管和间质液体间隙，3)确定 老化心脏对缺氧的脆弱性及其产生的能力 腺苷，以及4)确定腺苷的间质水平 随着年龄的增长和β-肾上腺素能刺激而改变。老龄化的重要性 5‘-核苷酸酶和腺苷脱氨酶的活性 分别负责腺苷的形成和分解 在灌流的心脏、分离的心肌细胞、血管平滑肌中进行研究 毛细血管内皮细胞。也谈衰老对细胞内的影响 腺苷水平、β-肾上腺素能受体结合特性和 激素敏感的腺苷环化酶将被研究。 这个项目代表了一种新的方法，旨在阐明一部小说和 导致成人心脏老化的重要机制 对β-肾上腺素能刺激的反应与其年轻的对应物一样。

The aged heart has a diminished response to Beta-adrenergic stimulation as compared to the young adult heart. Preliminary studies indicate that the aged heart produces much more adenosine than does the young adult heart. From our previous work it is well known that adenosine has an antiadrenergic action in the heart. The overall purpose of the proposed project is to study the role of adenosine in the reduced responsiveness of the aged adult heart to Beta-adrenergic stimulation. Hearts from progressively aged adult rats will be perfused to investigate the relationship between aging, adenosine production and the diminution of Beta-adrenergic contractile (extent and rate of pressure development) and metabolic (cyclic AMP, cyclic AMP-dependent protein kinase, protein phosphorylation, glycogen phosphoylase) variables. The role of adenosine in the decreased response of the aging adult heart to Beta adrenergic stimulation will be explored by, 1) determining the sensitivity of the aging heart to adenosine, 2) curtailing the build-up of adenosine in the vascular and interstitial fluid spaces of the aging heart, 3) ascertaining the vulnerability of the aging heart to hypoxia and its ability to produce adenosine, and 4) determining how the interstitial levels of adenosine change with aging and Beta-adrenergic stimulation. The importance of aging on the activities of 5'-nucleotidase and adenosine deaminase, the enzymes responsible for adenosine formation and breakdown, respectively, will be investigated in perfused hearts, isolated myocytes, vascular smooth muscle and capillary endothelium. Also the effect of aging on intracellular adenosine levels, Beta-adrenergic receptor binding characteristics and hormone sensitive adenylate cyclase will be studied. This project represents a new approach designed to elucidate a novel and important mechanism responsible for why the aging adult heart is not as responsive to Beta-adrenergic stimulation as its younger counterpart.