ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。与年龄相关的一氧化氮可用性降低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）产生不利影响的机制之一。有几个潜在的机制，其中一氧化氮的生产可能会减少与老化。然而，目前的动物和人类数据表明，增加氧化应激可能导致BH 4的绝对和/或相对减少，导致随后的一氧化氮生物利用度降低。由于年龄的增长与氧化应激水平的增加有关，因此可以合理地假设心血管功能的年龄相关变化可能至少部分是由于BH 4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，也可以合理地假设，与定期锻炼相关的更有利的心血管特征可能至少部分是由于BH 4的生物利用度更高。因此，本研究的具体目的是测量年轻人和老年人久坐不动的成年人以及接受耐力运动训练的老年人服用BH 4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.