Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

Abstract

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.

Peripheral Blood Flow Regulation in Human Obesity and Metabolic Syndrome

“…As noted above, we have not observed large group differences in measures of vascular function in young obese humans or adults with metabolic syndrome (31, 33, 34). However, recent data from our group suggest unique phenotypes exist within groups of obese individuals which appear to drive impairments in subclinical measures of vascular function.…”

“…Based on our work in resting humans (35), we hypothesized blood flow responses to acute exercise would be reduced in human obesity and/or metabolic syndrome. Surprisingly, and in direct contrast to data from animals, we have consistently found that young obese individuals and/or individuals with metabolic syndrome do not exhibit impairments in whole limb blood flow responses to acute exercise, and under certain conditions blood flow responses may actually be higher when compared to non-obese control subjects [Figure 3, (31, 33, 34)]. These data are not only in contrast with the majority of animal work, but also disagree with previous work conducted in humans (17, 27).…”

“…Specifically, blood flow is not uniformly distributed among and within working muscles (26) and the exact pattern of flow distribution is difficult to assess. With this in mind, we speculate preserved and/or increased whole-limb blood flow responses to exercise in human metabolic syndrome [Figure 3, (31, 33, 34)] may be the result of altered blood flow distribution. Impaired distribution, or greater blood flow to inactive skeletal muscle fibers and/or non-metabolically active tissues (e.g.…”

“…Additionally, our recent data support the idea that chronic inflammation plays a role in determining how quickly the blood flow response to exercise reaches steady-state (Figure 5A). Specifically, those individuals with high C-reactive protein levels (a measure of systemic inflammation) require more time to achieve steady-state exercise blood flow [Figure 5B, (33)]. Functionally, a delayed vasodilator response to exercise may result in earlier onset of fatigue and poor exercise tolerance (22), which has important clinical implications.…”

“…Functionally, a delayed vasodilator response to exercise may result in earlier onset of fatigue and poor exercise tolerance (22), which has important clinical implications. Interestingly, this impairment is reversed with acute infusion of Vitamin C (a potent antioxidant) (33). Collectively, these findings expose a potential relationship between inflammation, oxidative stress, and the time-course of the exercise vasodilator response in human obesity and metabolic syndrome (32, 33).…”