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.

Keywords: antioxidant; blood flow; reactive oxygen species.

Fig. 1.

Effect of acute ascorbic acid (AA) infusion on mean response time (MRT). A: change in forearm vascular conductance (FVC) averaged in 3-s bins during 5 min of dynamic forearm exercise. Data from a representative healthy control before AA infusion (Trial 1). B: Lean (n = 13), Obese (n = 10), metabolic syndrome (MetSyn) (n = 9). MRT was not different between groups (main effect of group: P = 0.26). MRT was not altered when AA was infused (Trial 2), compared with exercise alone (Trial 1) (main effect of AA: P = 0.50). C: change in MRT with AA infusion (Δ) was not different between groups (interaction between group and AA: P = 0.90) although individual responses were variable (a negative value indicates MRT decreased with AA infusion).

Fig. 2.

Effect of acute ascorbic acid infusion on the exercise-mediated increase in FVC. A: Lean (n = 14), Obese (n = 10), MetSyn (n = 13). The exercise-mediated increase FVC from rest (Δ, Exercise − Rest) was not altered when AA was infused (Trial 1, Min 15), compared with exercise alone (Trial 1, Min 5) (main effect of AA: P = 0.34), and responses were not different between groups (main effect of group: P = 0.16). B: change in the exercise-mediated increase in FVC with AA infusion was not different between groups (interaction between group and AA: P = 0.94) although individual responses were variable (a positive value indicates FVC increased after AA infusion). C: Lean (n = 15), Obese (n = 10), MetSyn (n = 14). The exercise-mediated increase in FVC from rest (Δ) was not different between groups (main effect of group, P = 0.31), and responses did not increase when AA was infused (Trial 2, Min 5), compared with exercise alone (Trial 1, Min 5) (main effect of AA: P = 0.93). D: change in the exercise-mediated increase in FVC with AA infusion was not different between groups (interaction between group and AA: P = 0.85) although individual responses were variable (a positive value indicates FVC increased after AA infusion).

Fig. 3.

Effect of inflammation on MRT and change with acute ascorbic acid infusion. A: C-reactive protein (CRP) <3 mg/l (n = 25), CRP >3 mg/l (n = 6). Consistent with clinical guidelines, those subjects with CRP levels >3 mg/l tended to exhibit longer baseline MRT (P = 0.09). B: those subjects with CRP levels >3 mg/l tended to exhibit a greater reduction in MRT (Δ) with ascorbic acid infusion (P = 0.07) compared with adults with CRP levels <3 mg/l. †P < 0.10 vs. CRP <3 mg/l.