Oxidative stress-related impairment of endothelial function in uncomplicated obesity

Abstract

Purpose: Visceral obesity is associated with vascular oxidative stress and development of hypertension. Therefore, we tested the hypothesis that suppression of vascular oxidative stress in adults with visceral obesity would improve endothelium-dependent dilation. Methods: IV infusion of a water-soluble antioxidant (ascorbic acid) was performed in 15 middle-age obese adults (3 men/12 women) without diabetes or hypertension in a placebo-controlled, double-blinded, crossover study design. Ascorbic acid was infused at 0.06g/kg fat free mass in 100 ml saline at 5 mL/min over 20 min (bolus) followed by a drip infusion at 0.02 g/kg fat-free mass in 30 ml saline at 0.5 mL/min over 60 min. Endothelium-dependent dilation was assessed via brachial artery flow-mediated dilation (FMD) and expressed as % increase in diameter from baseline before forearm occlusion. Results: Android fat distribution in the visceral cavity (VAT%) was 39 ± 10% and body mass index (BMI) was 37 ± 6 kg/m2. IV infusion significantly increased plasma ascorbic acid concentrations (Baseline: 42 ± 2 vs. Bolus: 66 ± 6 vs. End: 62 ± 4 μmol/L, P<0.001). Compared with baseline, bolus infusion of ascorbic acid significantly increased FMD (Baseline: 5.8 ± 2.5 vs. Bolus: 9.0 ± 4.0 vs. End: 8.0 ± 4.2 %, P=0.01), which remained after statistically adjusting for the stimulus (shear rate area under the curve) via analysis of covariance (P=0.04). No significant change in FMD was observed following placebo (saline) during a separate study visit (Baseline: 8.0 ± 4.4 vs. Bolus: 8.3 ± 3.9 vs. End: 8.6 ± 2.9 %, P=0.86). Conclusions: These preliminary findings suggest that acute elevations in plasma ascorbic acid concentrations improve endothelium-dependent dilation in middle-aged adults with visceral obesity. Future studies should target mechanisms by which mediators of oxidative stress in obesity (e.g., hyperlipidemia, hyperinsulinemia) inhibit nitric oxide-mediated vasodilation. Funding and support: R01HL159370-01 (S.W.H.). This work was also supported by a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute (# UL1TR002366). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or CTSA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.