ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。随着年龄的增长，一氧化氮的可获得性降低，这是增龄对心血管功能(如内皮依赖性血管扩张和动脉顺应性)产生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，这可能是几种潜在的机制。然而，目前的动物和人类数据提示，氧化应激增加可能会导致BH4的绝对和/或相对减少，从而导致一氧化氮生物利用度的下降。由于年龄的增加与氧化应激水平的增加有关，因此有理由假设与年龄相关的心血管功能变化可能至少部分是由于BH4生物活性的下降。相比之下，耐力运动训练与更有利的心血管功能和减少氧化应激水平有关。因此，也有理由假设，与定期运动相关的更有利的心血管状况可能至少部分归因于更大的BH4生物利用度。因此，这项研究的具体目的是测量服用BH4前后久坐不动的年轻人和接受耐力运动训练的老年人的心血管功能。

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.