title: FFA-induced endothelial dysfunction can be corrected by vitamin C.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, Vienna A-1090, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Pleiner
authors.forename: Georg
authors.initials: G
authors.lastname: Schaller
authors.forename: Friedrich
authors.initials: F
authors.lastname: Mittermayer
authors.forename: Michaela
authors.initials: M
authors.lastname: Bayerle-Eder
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006801:Humans; D008297:Male; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005230:Fatty Acids, Nonesterified; D014665:Vasodilator Agents; D000109:Acetylcholine; D001205:Ascorbic Acid