L-ARGININE SUPPLEMENTATION IN THE ELDERLY-NITRIC OXIDE

目前的实验证据表明，一氧化氮在维持正常血管功能和结构、血压、睡眠、食欲和性功能方面的重要性。同样清楚的是，一氧化氮活性在多种心血管疾病中受损，并且这种缺陷响应于L-精氨酸的施用，L-精氨酸是产生一氧化氮的唯一底物。已发表的动物研究和我们自己在人类中的初步发现表明，L-精氨酸水平随着年龄的增长而下降，因此可能对血管功能障碍和其他衰老特征的发展和进展构成可逆的贡献。我们还发现，在老年人中，营养L-精氨酸补充剂可以将血清L-精氨酸水平提高到与年轻受试者相当的水平，但这种作用的功能意义仍然未知。这项为期一年的试点提案旨在确定通过营养补充提高血清L-精氨酸水平是否会导致一氧化氮活性标志物的增加，增强内皮细胞、一氧化氮介导的血管扩张功能，并可能改善睡眠质量、白天警觉性和食欲的主观自我评估。这项工作可以为长期补充安全，廉价的药物，以保护老年人的心血管和其他功能的研究提供理论基础。

Current experimental evidence points to the importance of nitric oxide in the preservation of normal vascular function and structure, blood pressure, sleep, appetite, and sexual function. It is also clear that nitric oxide activity is impaired in a wide array of cardiovascular disorders and that this deficit responds to administration of L-arginine, the sole substrate for generation of nitric oxide. Published studies in animals and our own preliminary findings in humans show that L-arginine levels decline with aging and could thus constitute a reversible contributor to development and progression of vascular dysfunction and other features of aging. We have also found that in the elderly, nutritional L-arginine supplementation can raise serum L-arginine levels to values comparable to those in younger subjects, but the functional implications of this effect remain unknown. This one year pilot proposal seeks to determine whether raising serum L-arginine levels with nutritional supplementation leads to increases in markers of nitric oxide activity, enhances endothelial, nitric oxide-mediated vasodilator function, and possibly improves subjective self-assessments of quality of sleep, daytime alertness, and appetite. This work could provide a theoretical foundation for studies of longer term supplementation with safe, inexpensive agents which could preserve cardiovascular and other functions in the elderly.