Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress

Abstract

Older adults with cardiovascular disease exhibit microvascular dysfunction and increased levels of reactive oxygen species (ROS). We hypothesized that microvascular impairments begin early in the disease process and can be improved by scavenging ROS. Forearm blood flow (Doppler ultrasound) was measured in 45 young (32 ± 2 yr old) adults (n = 15/group) classified as lean, obese, and metabolic syndrome (MetSyn). Vasodilation in response to endothelial (ACh) and vascular smooth muscle [nitroprusside (NTP) and epoprostenol (Epo)] agonists was tested before and after intra-arterial infusion of ascorbic acid to scavenge ROS. Vasodilation was assessed as a rise in relative vascular conductance (ml·min(-1)·dl(-1)·100 mmHg(-1)). ACh and NTP responses were preserved (P = 0.825 and P = 0.924, respectively), whereas Epo responses were lower in obese and MetSyn adults (P < 0.05) than in lean controls. Scavenging of ROS via infusion of ascorbic acid resulted in an increase in ACh-mediated (P < 0.001) and NTP-mediated (P < 0.001) relative vascular conductance across all groups, suggesting that oxidative stress influences vascular responsiveness in adults with and without overt cardiovascular disease risk. Ascorbic acid had no effect on Epo-mediated vasodilation (P = 0.267). These results suggest that obese and MetSyn adults exhibit preserved endothelium-dependent vasodilation with reduced dependence on prostacyclin and are consistent with an upregulation of compensatory vascular control mechanisms.

Keywords: blood flow; endothelial function; nitric oxide; prediabetes; prostacyclin.

Fig. 1.

Increase in relative forearm vascular conductance (rFVC) from baseline with intra-arterial infusions. A: rFVC increased with increasing dose of ACh (main effect of dose, P < 0.001), and responses were not different between groups (group-dose interaction, P = 0.677). B: rFVC increased with increasing dose of nitroprusside (NTP; main effect of dose, P < 0.001), and responses were not different between groups (group-dose interaction, P = 0.638). C: rFVC increased with increasing dose of epoprostenol (Epo; main effect of dose, P < 0.001), and responses were greater in lean adults than in adults with metabolic syndrome (MetSyn) and obese adults (group-dose interaction, P = 0.049). Post hoc comparisons indicate differences at the following Epo doses: medium [lean vs. obese (P = 0.022)] and high [lean vs. obese (P < 0.001) and lean vs. MetSyn (P = 0.014)]. *P < 0.05 (group-dose interaction).

Fig. 2.

Change in rFVC response to ACh infusion with ascorbic acid (AA) infusion in lean (n = 14; A), obese (n = 15; B), and MetSyn (n = 15; C) groups. rFVC increased with ascorbic acid infusion (main effect of AA, P < 0.001); however, effect of AA on ACh-mediated vasodilation was not different between groups (group-AA interaction, P = 0.474). ‡P < 0.05 vs. pre-AA (main effect of AA).

Fig. 3.

Change in rFVC response to NTP infusion with ascorbic acid infusion in lean (A; n = 15), obese (n = 15; B), and MetSyn (C; n = 14) groups. rFVC increased with AA infusion (main effect of AA, P < 0.001). Effect of ascorbic acid on NTP-mediated vasodilation tended to be group-specific (group-ascorbic acid interaction, P = 0.051), with a trend for no effect of ascorbic acid on NTP responses in obese adults (B). ‡P < 0.05 vs. pre-AA (main effect of AA).

Fig. 4.

Change in rFVC response to Epo infusion with ascorbic acid infusion in lean (A; n = 13), obese (B; n = 14), and MetSyn (C; n = 14) groups. rFVC increased with increasing dose (main effect of dose, P < 0.001). There was no effect of AA infusion in any group (main effect of AA, P = 0.267; group-AA interaction, P = 0.831).