Vitamin C, diclophenac, and L-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in humans.
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.
Steer
Peter
P
Department of Medical Sciences/Internal Medicine, University Hospital, SE-75185 Uppsala, Sweden. Peter.Steer@medsci.uu.se
Millgård
Jonas
J
Basu
Samar
S
Lithell
Hans
H
Vessby
Bengt
B
Berne
Christian
C
Lind
Lars
L
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005260:Female; D005542:Forearm / Q000098:blood supply; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013548:Sweden; D024505:Tocopherols / Q000097:blood; D014280:Triglycerides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D017962:alpha-Linolenic Acid / Q000378:metabolism
D000925:Anticoagulants; D016861:Cyclooxygenase Inhibitors; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D016166:Free Radical Scavengers; D014280:Triglycerides; D017962:alpha-Linolenic Acid; D004008:Diclofenac; D006493:Heparin; D001120:Arginine; D001205:Ascorbic Acid; D024505:Tocopherols