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Vitamin C, diclophenac and L-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in humans
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Clinical Nutrition)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Geriatrics)
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2003 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 168, no 1, 65-72 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
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
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90411DOI: 10.1016/S0021-9150(03)00023-6PubMedID: 12732388OAI: oai:DiVA.org:uu-90411DiVA: diva2:162755
Available from: 2003-05-06 Created: 2003-05-06 Last updated: 2010-08-11Bibliographically approved
In thesis
1. Lipids and Endothelium-Dependent Vasodilation
Open this publication in new window or tab >>Lipids and Endothelium-Dependent Vasodilation
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Lipider och endotelberoende vasodilatation
Abstract [en]

Impaired endothelium-dependent vasodilation (EDV) is associated with atherosclerotic cardiovascular disease as well as several of its risk factors.

The aim of the present thesis was to investigate how lipids influence EDV in the vascular bed of the human forearm.

Apolipoprotein B was inversely associated with both EDV and endothelium-independent vasodilation (EIDV) in healthy subjects aged 20-69 years. HDL cholesterol was associated with the EDV to EIDV ratio (EFI). Small LDL particles and antibodies against oxidized LDL were not associated with endothelial vasodilatory function.

The EFI in young, healthy subjects was positively associated with alpha-linolenic acid proportion, but inversely associated with myristic acid in men only. Eicosapentaenoic acid was positively associated with EDV, whereas dihomo-gamma-linolenic acid was inversely associated with both EDV and EIDV in men.

Acute elevation of long-chain fatty acids with Intralipid®/heparin infusion in young, healthy subjects impaired EDV after 2 h. This impairment could be prevented by co-infusing vitamin C, diclophenac or L-arginine. Acute elevation of both medium-chain and long-chain fatty acids during Structolipid®/heparin infusion did not impair EDV.

An ordinary meal (34 E% fat) transiently attenuated EDV at 1 hour. No attenuation in EDV was observed after meals containing 20 and 3 E% fat.

These findings show that the endothelial vasodilatory function is associated with fatty acid profile in serum in the fasting state and during acute fatty acid elevation, as well as with apolipoprotein B and HDL cholesterol. Furthermore, lowering dietary fat content to 20 E% or less preserves endothelial vasodilatory function and might therefore protect against atherosclerosis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 78 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1263
Keyword
Medicine, Atherosclerosis, endothelium, vasodilation, nitric oxide, fatty acid, meal, diet, lipoprotein, cyclooxygenase, diclophenac, L-arginine, LDL, human, Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Internal Medicine
Identifiers
urn:nbn:se:uu:diva-3424 (URN)91-554-5633-2 (ISBN)
Public defence
2003-05-26, Aulan, Thoraxhuset - ingång 50, Akademiska sjukhuset, Uppsala, 09:15
Opponent
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Available from: 2003-05-06 Created: 2003-05-06 Last updated: 2010-10-21Bibliographically approved

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Steer, PeterBasu, SamarVessby, BengtBerne, ChristianLind, Lars

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