title: [Effects of free fatty acids on nitric oxide synthase activity and mRNA expression in endothelial cell of SD rat aorta].
abstract: OBJECTIVE
  To test the hypothesis that free fatty acids (FFA) induced endothelial dysfunction might relate with the inhibitions of endothelial nitric oxide synthase (eNOS) mRNA expression and activity, and to explore the possible pathogenic mechanisms.
  
  
  METHODS
  Male SD rats underwent 6 h infusion in two groups: Normal control (NC, n=20) infused with saline; FFA group (n=20) infused with 20% intralipid + heparin. Blood samples were collected at the end of infusion so as to measure the concentrations of FFA, nitrogen oxides (NOx), reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH) and high sensitivity C-reactive protein (hs-CRP). The eNOS activity and mRNA expression were analyzed with aortic endothelial homogenate.
  
  
  RESULTS
  In FFA group, the plasma FFA concentration was higher [(1146.4+/-336.6) micromol/L vs (345.5+/-113.6) micromol/L, P<0.01] while the NOx level was lower [(14.3+/-1.9) micromol/L vs (19.3+/-2.9) micromol/L, P<0.01]. The serum concentrations of ROS, MDA, hs-CRP were elevated in FFA group when compared with controls [ROS: (864.3+/-135.4) mmol/L vs (452.4+/-90.5) mmol/L, P<0.05; MDA: (8.05+/-1.69) nmol/L vs (5.53+/-0.43) noml/L, P<0. 05; hs-CRP: (0.35+/-0.04) mg/L vs (0.21+/-0.03) mg/L, P<0.053] while GSH level was significantly declined in FFA group [(153.1+/-55.9) mg/L vs (171.9+/-60.5) mg/L, P<0.05]. Both the eNOS mRNA level and eNOS activity in endothelial homogenate were decreased in FFA group [eNOS mRNA/beta-actin: 1.42 vs 2.12, P<0.01; eNOS activity: (1.15+/-0.42) pmol/(min x mg) vs (2.43+/-0.56) pmol/(min x mg), P<0.01].
  
  
  CONCLUSIONS
  The eNOS mRNA expression and activity may be inhibited by elevated circulating FFAs concentration, of which mechanisms may be related to the increased oxidative stress and moderate inflammation.
authors.affiliation: Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Ye-Rong
authors.initials: YR
authors.lastname: Yu
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Li
authors.forename: Xiang-Xun
authors.initials: XX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology*; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005230:Fatty Acids, Nonesterified; D009589:Nitrogen Oxides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D002097:C-Reactive Protein; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione