FFA-induced endothelial dysfunction can be corrected by vitamin C

Insulin resistance is associated with an inappropriate elevation of plasma FFA and endothelial dysfunction. FFA could stimulate formation of reactive oxygen species, which could be responsible for vascular impairment. In this randomized, double-blind, cross-over study in 10 healthy volunteers (24 +/...

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Published in:The journal of clinical endocrinology and metabolism 2002-06, Vol.87 (6), p.2913-2917
Main Authors: PLEINER, Johannes, SCHALLER, Georg, MITTERMAYER, Friedrich, BAYERLE-EDER, Michaela, RODEN, Michael, WOLZT, Michael
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Antioxidants - pharmacology
Ascorbic Acid - pharmacology
Biological and medical sciences
Cross-Over Studies
Double-Blind Method
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiopathology
Fatty Acids, Nonesterified - blood
General and cellular metabolism. Vitamins
Humans
Male
Medical sciences
Pharmacology. Drug treatments
Vasodilation - physiology
Vasodilator Agents - pharmacology
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Summary:Insulin resistance is associated with an inappropriate elevation of plasma FFA and endothelial dysfunction. FFA could stimulate formation of reactive oxygen species, which could be responsible for vascular impairment. In this randomized, double-blind, cross-over study in 10 healthy volunteers (24 +/- 3 yr old), forearm blood flow (FBF) responses to intraarterial acetylcholine (ACh) and glyceryl trinitrate were assessed with coadministration of vitamin C (24 mg/ml) or placebo, respectively, in the presence of increased plasma FFA induced by Intralipid/heparin infusion. The rise in plasma FFA from 320 +/- 64 to 1852 +/- 232 micromol/liter was associated with a reduced response of FBF to ACh by 55% (P < 0.01). During coadministration of vitamin C, the impaired responsiveness of FBF to ACh was completely reversed and not different from that observed under baseline conditions. Vitamin C did not affect plasma FFA concentrations. Glyceryl trinitrate responsiveness was unchanged during FFA elevation, with or without vitamin C. These data suggest that FFA-induced vascular oxidative stress could contribute to endothelial dysfunction in insulin-resistant patients. High concentrations of antioxidants are able to reverse the local effects of FFA on endothelium-dependent vasodilation.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.87.6.2913