title: Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okuda
authors.forename: K
authors.initials: K
authors.lastname: Kawashima
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: K
authors.initials: K
authors.lastname: Tsurumaru
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Soma
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Yamashita
mesh_terms: D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D013012:Sorbitol / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D002147:Calmodulin; D005231:Fatty Acids, Unsaturated; D013449:Sulfonamides; D009569:Nitric Oxide; D013012:Sorbitol; D013395:Sucrose; C017967:W 7; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D005947:Glucose; D002118:Calcium