Palmitic acid but not stearic acid inhibits NO-production in endothelial cells.
Several studies showed a diminished production of the endothelium-derived relaxing factor nitric oxide (NO) in the early stage of atherosclerosis. The inhibition of NO-production seems to be mediated by lipoproteins, especially oxidized low-density lipoproteins (ox-LDL). There is some evidence, that the interactions of lipoproteins and NO are associated with the phospholipid fraction of lipoproteins. Since fatty acids have different atherogenic properties-depending on chain length, degree of saturation and steric configuration-, we investigated the effect of fatty acids on endothelial NO-production. Human umbilical vein endothelial cells were incubated with palmitic acid and stearic acid in different concentrations in culture medium enriched with serum albumin for five hours. After that, NO-production was stimulated by calcium-ionophore A23187. NO-production was determined by a bioassay method using RFL-6 cells followed by radioimmunological determination of cGMP. NO-production stimulated by calcium-ionophore A23187(100%) was decreased by palmitic acid (10, 50, 100 microM) to 79 +/- 12%; 63 +/- 10% and 53 +/- 14%. In contrast, incubation with stearic acid (10, 50 and 100 microM) had no effect on A23187-stimulated NO-production (94 +/- 11%; 93 +/- 11%; 104 +/- 15%). Thus, palmitic acid but not stearic acid dose-dependently inhibited NO-release by endothelial cells. These different actions parallel the differing atherogenic potential of the two fatty acids.
Moers
A
A
Dpt. Physiology and Biochemistry of Nutrition, Federal Research Centre, Kiel.
Schrezenmeir
J
J
D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019308:Palmitic Acid / Q000494:pharmacology*; D013229:Stearic Acids / Q000494:pharmacology*; D014471:Umbilical Veins
D003470:Culture Media; D013229:Stearic Acids; D019308:Palmitic Acid; D009569:Nitric Oxide; D000001:Calcimycin; C031183:stearic acid; D006152:Cyclic GMP