Abstract
INTRODUCTION: Evidence suggests that ascorbic acid improves function of the vascular endothelium via suppression of oxidative stress. Therefore, we tested the hypothesis that ascorbic acid (AA, a water-soluble antioxidant) would prevent lipid-mediated reductions in function of the vascular endothelium via antioxidant properties. METHODS: A 20% IV fat emulsion (Intralipid) was administered for two hours to eight healthy, middle-aged adults (two men/six women) with and without co-infusion of AA (separate visits) in a double-blinded, crossover study design. Endothelium-dependent dilation was assessed via brachial artery flow-mediated dilation and immunocytochemistry was used to assess oxidative stress (nitrotyrosine) and phosphorylated endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). RESULTS: Within 20 min of infusion, Intralipid increased plasma fatty acid concentration (+36 ± 18 μmol/L, P<0.05) and significantly reduced flow-mediated dilation (−53%, P<0.05). In contrast to our hypothesis, co-infusion of AA did not prevent the reduction in flow-mediated dilation (−41%, P<0.05). In HUVECs, AA did not prevent the increase in oxidative stress following incubation with lipid (Lipid: +53% vs. Lipid+AA: +35%). An increase in phosphorylated eNOS was observed with incubation of both AA (+28%) and lipid+AA (+24%). CONCLUSIONS: These preliminary findings suggest that increased oxidative stress and impaired function of the vascular endothelium via fatty acids cannot be prevented by ascorbic acid despite increased phosphorylated eNOS.