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.

Nyckelord

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

MEDICINE

MEDICIN

Publikations- och innehållstyp

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