Vitamin C, diclophenac and L-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in humans
2003 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 168, no 1, 65-72 p.Article in journal (Refereed) Published
An acute elevation of circulating non-esterified fatty acids (NEFAs) has previously been shown to impair endothelium-dependent vasodilation (EDV). In this study, we investigated if local administration of vitamin C (n=8, 18 mg/min), L-arginine (n=8, 12.5 mg/min), or the cyclooxygenase (COX) inhibitor diclophenac (n=8, 0.5 mg/min) can counteract the endothelial dysfunction seen during infusion of Intralipid plus heparin (n=10). EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (Mch; 2 and 4 microg/min) and sodium nitroprusside (SNP; 5 and 10 microg/min). Forearm blood flow (FBF) was determined with venous occlusion plethysmography. Intralipid and heparin increased circulating NEFA levels sevenfold and impaired EDV (P<0.001 vs baseline). Concomitant administration of L-arginine or diclophenac abolished the NEFA-induced impairment in EDV. Concomitant vitamin C administration actually improved EDV (P<0.05 vs baseline). NEFA elevation increased EIDV (P<0.01), but this effect was not significant after L-arginine or diclophenac infusions. In conclusion, an acute elevation of circulating NEFAs led to impaired EDV. Administration of L-arginine, vitamin C or COX inhibition abolished this effect, suggesting that NEFAs might interact with endothelial vasodilatory function through multiple mechanisms.
Place, publisher, year, edition, pages
2003. Vol. 168, no 1, 65-72 p.
Adult, Anticoagulants/pharmacology, Arginine/*pharmacology, Ascorbic Acid/*pharmacology, Comparative Study, Cyclooxygenase Inhibitors/*pharmacology, Diclofenac/*pharmacology, Endothelium; Vascular/*drug effects/*physiology, Fat Emulsions; Intravenous/pharmacology, Fatty Acids; Nonesterified/blood/*metabolism, Female, Forearm/blood supply, Free Radical Scavengers/*pharmacology, Heparin/pharmacology, Humans, Infusions; Intravenous, Male, Reference Values, Regional Blood Flow/drug effects/physiology, Sweden, Tocopherols/blood, Triglycerides/metabolism, Vasodilation/*drug effects/*physiology, alpha-Linolenic Acid/metabolism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-90411DOI: 10.1016/S0021-9150(03)00023-6PubMedID: 12732388OAI: oai:DiVA.org:uu-90411DiVA: diva2:162755