ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。年龄相关的一氧化氮可用性下降构成了年龄增长对人类心血管功能（即内皮依赖性血管舒张和动脉顺应性）不利影响的机制之一。随着年龄的增长，一氧化氮的产生可能会减少，有几种潜在的机制。然而，目前的动物和人类数据表明，氧化应激的增加可能导致BH4的绝对和/或相对减少，导致随后一氧化氮生物利用度的降低。由于年龄的增长与氧化应激水平的增加有关，因此有理由假设年龄相关的心血管功能变化可能（至少部分）是由于BH4生物活性的降低。相比之下，耐力运动训练与更有利的心血管功能和降低氧化应激水平有关。因此，我们也可以合理地假设，与定期运动相关的更有利的心血管状况可能，至少在一定程度上，是由于BH4的生物利用度更高。因此，本研究的具体目的是测量年轻和老年久坐的成年人以及耐力训练的老年人在给予BH4前后的心血管功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The age-related decrease in nitric oxide availability constitutes one of the mechanisms by which advancing age adversely affects the cardiovascular function (i.e. endothelial dependent vasodilation and arterial compliance) in humans. There are several potential mechanisms by which nitric oxide production may be reduced with aging. However, current animal and human data sugesst that increased oxidative stress may lead to an absolute and/or relative decrease in BH4, leading to a subsequent decrease in nitric oxide bioavailability. Because advancing age is associated with increased oxidative stress level, it is resonable to hypothesis that the age related changes in cardiovascular function may be, at least in part, due to a decrease in BH4 bioactivity. In contrast, endurance exercise training is associated with a more favorable cardiovascular function and decreased oxydative stress level. Therefore, it is also resonable to hypothesize that the more favorable cardiovascular profile associated with regular exercise may be, at least in part, due to a greater BH4 bioavailability. Consequently, the specific aim of this study is to measure the caridovascular function before and after administering BH4 in young and older sedentary adults and in endurance exercise-trained older adults.