Skip to main content
SpringerLink
Log in

Acute elevations of medium-and long-chain fatty acids have different impacts on endothelium-dependent vasodilation in humans

  • Articles
  • Published:
Lipids

Abstract

It has previously been shown that acute elevation of long-chain fatty acids (LCFA) impairs endothelium-dependent vasodilation (EDV) in humans. In this study, we tested the hypothesis that an elevation of both medium-chain fatty acids (MCFA) and LCFA affects the endothelium differently from LCFA elevation alone. Ten healthy volunteers received an intravenous infusion of Structolipid≿ (structured TG, MCFA/LCFA ratio 1∶1) and heparin for 2 h, while another 10 subjects received an infusion of Intralipid≿ (LCFA only) and heparin. EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (2 and 4 μg/min) and sodium nitroprusside (5 and 10 μg/min). Forearm blood flow was determined by venous occlusion plethysmography. Intralipid and heparin increased circulating FA levels from 0.2±0.1 to 1.4±0.5 mmol/L (P<0.001) and reduced EDV by 20% (P<0.01). Although Structolipid and heparin increased circulating FA levels to a similar extent (from 0.4±0.1 to 1.8±0.4 mmol/L after 2 h), EDV was not significantly changed. EIDV increased slightly during both interventions (P<0.05). In conclusion, an acute elevation of LCFA attenuated EDV, whereas an elevation of both MCFA and LCFA did not influence EDV. Thus, FA composition seems to be of importance for EDV in healthy humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

COX:

cyclooxygenase

EDV:

endothelium-dependent vasodilation

EIDV:

endothelium-independent vasodilation

FBF:

forearm blood flow

LCFA:

long-chain fatty acids

MCFA:

medium-chain fatty acids

Mch:

methacholine chloride

NEFA:

nonesterified fatty acids

PG:

prostaglandin

RIA:

radioimmunoassay

SNP:

sodium nitroprusside

TX:

thromboxane

VSMC:

vascular smooth muscle cell

References

  1. Steinberg, H.O., Tarshoby, M., Monestel, R., Hook, G., Cronin, J., Johnson, A., Bayazeed, B., and Baron, A.D. (1997) Elevated Circulating Free Fatty Acid Levels Impair Endothelium-Dependent Vasodilation, J. Clin. Invest. 100, 1230–1239.

    Article  PubMed  CAS  Google Scholar 

  2. Lundman, P., Eriksson, M., Schenck-Gustafsson, K., Karpe, F., and Tornvall, P. (1997) Transient Triglyceridemia Decreases Vascular Reactivity in Young, Healthy Men Without Risk Factors for Coronary Heart Disease, Circulation 96, 3266–3268.

    PubMed  CAS  Google Scholar 

  3. Lind, L., Fugmann, A., Branth, S., Vessby, B., Millgård, J., Berne, C., and Lithell, H. (2000) The Impairment in Endothelial Function Induced by Non-esterified Fatty Acids Can Be Reversed by Insulin, Clin. Sci. 99, 169–174.

    Article  PubMed  CAS  Google Scholar 

  4. de Kreutzenberg, S.V., Crepaldi, C., Marchetto, S., Calo, L., Tiengo, A., Del Prato, S., and Avogaro, A. (2000) Plasma Free Fatty Acids and Endothelium-Dependent Vasodilation: Effect of Chain-Length and Cyclooxygenase Inhibition, J. Clin. Endocrinol. Metab. 85, 793–798.

    Article  PubMed  Google Scholar 

  5. Paolisso, G., Gambardella, A., Tagliamonte, M.R., Saccomanno, F., Salvatore, T., Gualdiero, P., D’Onofrio, M.V., and Howard, B.V. (1996), Does Free Fatty Acid Infusion Impar Insulin Action Also Through an Increase in Oxidative Stress? J. Clin. Endocrinol. Metab. 81, 4244–4248.

    Article  PubMed  CAS  Google Scholar 

  6. Sarabi, M., Vessby, B., Millgård, J., and Lind, L. (2001) Endothelium-Dependent Vasodilation Is Related to the Fatty Acid Composition of Serum Lipids in Healthy Subjects, Atherosclerosis 156, 349–355.

    Article  PubMed  CAS  Google Scholar 

  7. Ignarro, L.J., Harbison, R.G., Wood, K.S., and Kadowitz, P.J. (1986) Activation of Purified Soluble Guanylate Cyclase by Endothelium-Derived Relaxing Factor from Intrapulmonary Artery and Vein: Stimulation by Acetylcholine, Bradykinin and Arachidonic Acid, J. Pharmacol. Exp. Ther. 237, 893–900.

    PubMed  CAS  Google Scholar 

  8. Moers, A., and Schrezenmeir, J. (1997) Palmitic Acid but Not Stearic Acid Inhibits NO-Production in Endothelial Cells, Exp. Clin. Endocrinol. Diabetes 105, 78–80.

    PubMed  CAS  Google Scholar 

  9. Davda, R.K., Stepniakowski, K.T., Lu, G., Ullian, M.E., Goodfriend, T.L., and Egan, B.M. (1995) Oleic Acid Inhibits Endothelial Nitric Oxide Synthase by a Protein Kinase C-Independent Mechanism, Hypertension 26, 764–770.

    PubMed  CAS  Google Scholar 

  10. Miettinen, T.A., Naukkarinen, V., Huttunen, J.K., Mattila, S., and Kumlin, T. (1982) Fatty-Acid Composition of Serum Lipids Predicts Myocardial Infarction, Br. Med. J. 285, 993–996.

    Article  CAS  Google Scholar 

  11. Öhrvall, M., Berglund, L., Salminen, I., Lithell, H., Aro, A., and Vessby, B. (1996) The Serum Cholesterol Ester Fatty Acid Composition but Not the Serum Concentration of α-Tocopherol Predicts the Development of Myocardial Infarction in 50-Year-Old Men: 19 Years Follow-up, Atherosclerosis 127, 65–71.

    Article  PubMed  Google Scholar 

  12. Lind, L., Sarabi, M., and Millgård, J. (1998) Methodological Aspects of the Evaluation of Endothelium-Dependent Vasodilation in the Human Forearm, Clin. Physiol. 18, 81–87.

    Article  PubMed  CAS  Google Scholar 

  13. Lind, L., Hall, J., Larsson, A., Annuk, M., Fellström, B., and Lithell, H. (2000) Evaluation of Endothelium Dependent Vasodilation in the Human Peripheral Circulation, Clin. Physiol 20, 440–448.

    Article  PubMed  CAS  Google Scholar 

  14. Boberg, M., Croon, L.B., Gustafsson, I.B., and Vessby, B. (1985) Platelet Fatty Acid Composition in Relation to Fatty Acid Composition in Plasma and to Serum Lipoprotein Lipids in Healthy Subjects with Special Reference to the Linoleic Acid Pathway, Clin. Sci. 68, 581–587.

    PubMed  CAS  Google Scholar 

  15. Öhrvall, M., Tengblad, S., and Vessby, B. (1993) Lower Tocopherol Serum Levels in Subjects with Abdominal Adiposity, J. Intern. Med. 234, 53–60.

    Article  PubMed  Google Scholar 

  16. Thurnham, D.I., Davies, J.A., Crump, B.J., Situnayake, R.D., and Davis, M. (1986) The Use of Different Lipids to Express Serum Tocopherol: Lipid Ratios for the Measurement of Vitamin E Status, Ann. Clin. Biochem. 23, 514–520.

    PubMed  CAS  Google Scholar 

  17. Basu, S. (1998) Radioimmunoassay of 8-Iso-prostaglandin F2α: An Index for Oxidative Injury via Free Radical Catalysed Lipid Peroxidation, Prostaglandins Leukot. Essent. Fatty Acids 58, 319–325.

    Article  PubMed  CAS  Google Scholar 

  18. Wu, G.H., Jarstrand, C., and Nordenstrom, J. (1999) Phagocyte-Induced Lipid Peroxidation of Different Intravenous Fat Emulsions and Counteractive Effect of Vitamin E, Nutrition 15, 359–364.

    Article  PubMed  CAS  Google Scholar 

  19. Shimokawa, H., and Vanhoutte, P.M. (1989) Dietary Omega 3 Fatty Acids and Endothelium-Dependent Relaxations in Porcine Coronary Arteries, Am. J. Physiol. 256, H968–H973.

    PubMed  CAS  Google Scholar 

  20. Juan, H., and Sametz, W. (1986) Vasoconstriction Induced by Noradrenaline and Angiotensin II Is Antagonized by Eicosapentaenoic Acid Independent of Formation of Trienoic Eicosanoids, Naunyn Schmiedebergs Arch. Pharmacol. 332, 288–292.

    Article  PubMed  CAS  Google Scholar 

  21. Miller, V.M., and Vanhoutte, P.M. (1985) Endothelium-Dependent Contractions to Arachidonic Acid Are Mediated by Products of Cyclooxygenase, Am. J. Physiol. 248, H432–H437.

    PubMed  CAS  Google Scholar 

  22. Kontos, H.A., Wei, E.P., Ellis, E.F., Jenkins, L.W., Povlishock, J.T., Rowe, G.T., and Hess, M.L. (1985) Appearance of Superoxide Anion Radical in Cerebral Extracellular Space During Increased Prostaglandin Synthesis in Cats, Circ. Res. 57, 142–151.

    PubMed  CAS  Google Scholar 

  23. Beckman, J.S., and Koppenol, W.H. (1996) Nitric Oxide. Superoxide, and Peroxynitrite: The Good, the Bad, and Ugly, Am. J. Physiol. 271, C1424-C1437.

    PubMed  CAS  Google Scholar 

  24. Taddei, S., Virdis, A., Ghiadoni, L., Magagna, A., and Salvetti, A. (1997) Cyclooxygenase Inhibition Restores Nitric Oxide Activity in Essential Hypertension, Hypertension 29, 274–279.

    PubMed  CAS  Google Scholar 

  25. Bouchard, J.F., and Lamontagne, D. (1999) Mechanisms of Protection Afforded by Cyclooxygenase Inhibitors to Endothelial Function Against Ischemic Injury in Rat Isolated Hearts, J. Cardiovasc. Pharmacol. 34, 755–763.

    Article  PubMed  CAS  Google Scholar 

  26. Steer, P., Millgård, J., Basu, S., Lithell, H., Vessby, B., Berne, C., and Lind, L., Vitamin C, Diclophenac, and l-Arginine Protect Endothelium-Dependent Vasodilation Against Elevated Circulating Fatty Acid Levels in Humans, Atherosclerosis (in press).

  27. de Man, F.H., Weverling-Rijnsburger, A.W., van der Laarse, A., Smelt, A.H., Jukema, J.W., and Blauw, G.J. (2000) Not Acute but Chronic Hypertriglyceridemia Is Associated with Impaired Endothelium-Dependent Vasodilation: Reversal After Lipid-Lowering Therapy by Atorvastatin, Arterioscler. Thromb. Vasc. Biol. 20, 744–750.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Sciences/Internal Medicine, University Hospital, SE-751 85, Uppsala, Sweden

    Peter Steer, Christian Berne & Lars Lind

  2. Department of Public Health and Caring Sciences/Geriatrics, University Hospital, SE-751 85, Uppsala, Sweden

    Samar Basu, Hans Lithell & Bengt Vessby

Authors
  1. Peter Steer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samar Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Lithell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bengt Vessby
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Berne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars Lind
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Steer.

About this article

Cite this article

Steer, P., Basu, S., Lithell, H. et al. Acute elevations of medium-and long-chain fatty acids have different impacts on endothelium-dependent vasodilation in humans. Lipids 38, 15–19 (2003). https://doi.org/10.1007/s11745-003-1025-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-003-1025-9

Keywords

Search

Navigation