MECHANISMS OF AGING--ENHANCED HEART ADENOSINE

衰老机制——增强心脏腺苷

• 批准号: 3123415
• 负责人: JAMES G DOBSON
• 金额: $ 17.48万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3123415
• 关键词: adenosine; adenylate cyclase; aging; atrial natriuretic peptide; beta adrenergic agent; cyclic AMP; heart contraction; heart metabolism; high performance liquid chromatography; intracardiac pressure; isolation perfusion; laboratory rat; muscle stimulant; myocardial ischemia /hypoxia; phosphorylation; protein kinase; vasodilation

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.

老年心脏对β-肾上腺素能刺激的反应降低 与年轻人的心脏相比 这个实验室的研究表明 老年心脏产生更多的腺苷， 腺苷水平。 这被认为是促进增强的抗肾上腺素能 腺苷的作用，反过来，降低老年人的反应性 心脏对β肾上腺素能刺激的反应 建议的目的 一个项目是确定为什么老年人的心脏产生更多的腺苷 并具有较高的核苷间质水平。 灌流大鼠 心脏也将用于研究代谢机制 负责增加生产腺苷的老化 心肌 衰老对腺苷摄取和代谢的影响将 用灌注心脏进行研究。 腺苷释放的影响， 将使用心室肌细胞进一步研究摄取和代谢 以及老年心脏的内皮细胞来描述衰老是如何影响 这些过程。 这个项目代表了一个相对较新的概念 涉及腺苷，这可能是重要的，在解释减少 哺乳动物心脏的β-肾上腺素能反应性， 衰老