Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells

Biochem Biophys Res Commun. 1997 Mar 17;232(2):487-91. doi: 10.1006/bbrc.1997.6328.


It is unclear whether the abnormal relaxation seen in diabetes is due to decreased levels of nitric oxide (NO) and how eicosapentaenoic acid (EPA, C20:5 omega 3) affects the endothelial production of NO. We investigated the effects of EPA ethyl ester (EPA-E) and elevated glucose on NO production by human endothelial cells (HUE). EPA-E (0.3 mM) significantly enhanced [NO2] production and the intracellular concentration of free Ca2+ within 3 min after EPA-E was added to the cultures. High levels of glucose (27.5 mM) significantly increased endothelial glucose, sorbitol and fructose, and inhibited [NO2-] production. However, EPA-E (0.3 mM) prevented the inhibition of [NO2-] production due to the activation of the Ca(2+)-calmodulin system of NO synthase. EPA-E decreased the glucose-mediated inhibition of NO production by HUE. These results suggest this agent might ameliorate endothelial dysfunction associated with diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calmodulin / antagonists & inhibitors
  • Cells, Cultured
  • Eicosapentaenoic Acid / analogs & derivatives
  • Eicosapentaenoic Acid / pharmacology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Fatty Acids, Unsaturated / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology
  • Humans
  • Nitric Oxide / biosynthesis*
  • Sorbitol / metabolism
  • Sucrose / metabolism
  • Sulfonamides / pharmacology
  • Umbilical Veins


  • Calmodulin
  • Fatty Acids, Unsaturated
  • Sulfonamides
  • Nitric Oxide
  • Sorbitol
  • Sucrose
  • W 7
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid
  • Glucose
  • Calcium