| Decreased flow-mediated dilation (FMD) and large artery compliance are two of the most important CV changes with aging. However, the mechanistic contribution of oxidative stress in impaired FMD and large artery compliance with age is unknown. Accordingly, two main studies were conducted to determine this.; For the first study, the specific aims were to determine if: (1) oxidative stress plays a role in the reduction in brachial artery FMD with age in sedentary adults, (2) brachial artery FMD is preserved with age in habitually exercising adults, (3) reduced oxidative stress plays a role in the maintenance of brachial artery FMD with age in exercising adults, (4) chronic ascorbic acid (vitamin C) supplementation will improve FMD in sedentary older adults. At baseline, FMD was ∼45% lower in the older vs. young sedentary men, but was preserved in older exercising men. Ascorbic acid infusion restored FMD in the sedentary older men, but did not affect FMD in the other 2 groups. Baseline plasma endothelin-1 concentration and was positively related to changes in FMD with ascorbic acid infusion. Oral ascorbic acid supplementation did not affect FMD in any group. These results provide the first evidence for an important role of oxidative stress in both the marked impairment in peripheral conduit artery FMD with sedentary human aging, and the preservation of FMD with physically active aging.; For the second study, the specific aims were to determine if: (1) oxidative stress tonically modulates large elastic artery compliance in healthy men, and (2) oxidative stress contributes to the age-related decline in arterial compliance, and consequently increased central arterial blood pressure in healthy men, and (3) improvement in arterial compliance can be obtained with chronic oral vitamin C supplementation. At baseline, carotid artery compliance was 43% lower and pulse wave velocity and augmentation index were higher in the older men. Neither vitamin C infusion nor chronic oral supplementation affected any cardiovascular function. The results from this study suggest that oxidative stress is not an important mechanism determining large elastic artery compliance in healthy men, nor does it contribute to adverse age-associated changes in central arterial compliance or BP. |
