| Description |
The overall objective of this dissertation was to further elucidate alterations in vascular function with age in healthy humans by utilizing the passive leg movement (PLM) model, with and without a posture-induced increase in femoral perfusion pressure (FPP), to assess nitric oxide (NO) bioavailability. In the first study, we examined the central and peripheral hemodynamic responses to PLM in young and old women. We observed a two- to three-fold attenuation in the leg blood flow (LBF) and leg vascular conductance (LVC) responses to PLM in the old women compared to the young women. These findings indicate that, similar to men, aging significantly attenuates vascular function in healthy women. The second study investigated the possible impact of elevated physical activity and fitness on the attenuated vascular function with age. Utilizing PLM, we documented that older individuals who remained physically active displayed improved vascular function compared to their sedentary age-matched counterparts, although not achieving the same vascular function as young sedentary individuals. In this study, we took these findings one step further by examining elite endurance trained older subjects and found that while they too demonstrated improved vascular function compared to sedentary age-matched subjects, vascular function failed to be restored to the level observed in the young, suggesting that there may be a ceiling effect whereby increasing physical activity yields diminishing returns in terms of vascular health. The third study sought to determine the role that oxidative stress may play in the age-related attenuation in vascular function by administering both a placebo and an oral antioxidant cocktail (AOC) in a single-blind cross-over design. In the placebo condition, the old subjects once again had an attenuated vasodilatory response to PLM. Although displaying greater inflammation than the young, the old did not clearly exhibit elevated markers of oxidative stress or decreased markers of antioxidant defenses. The AOC significantly improved antioxidant status and decreased lipid peroxidation in both the young and old. However, the AOC had no effect on the vasodilatory response to PLM in either group. Therefore, vascular dysfunction persisted in the older adults despite an AOC-induced increase in antioxidant status and attenuated oxidative stress, questioning the role of redox balance in the apparent age-related decrease in PLM-induced vasodilation. Collectively, this research has provided significant insight into the impact of aging in women, physical activity, and oxidative stress on alterations in NO-mediated vascular function across the lifespan. |
