ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING

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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.