title: Aspirin protected against endothelial damage induced by LDL: role of endogenous NO synthase inhibitors in rats.
abstract: OBJECTIVE
  To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level.
  
  
  METHODS
  Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-alpha), and the activity of dimethylaminohydrolase (DDAH) were measured.
  
  
  RESULTS
  A single injection of LDL (4 mg/kg) significantly decreased vasodilator responses to ACh, increased the serum level of ADMA, MDA, and TNF-alpha, and decreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses to ACh by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspirin group. Aspirin inhibited the increased level of MDA and TNF-alpha induced by LDL. Aspirin at the dose of 30 mg/kg, but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity of DDAH.
  
  
  CONCLUSIONS
  Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicited by LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentration by increasing DDAH activity.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Deng
authors.forename: Pan-yue
authors.initials: PY
authors.lastname: Deng
authors.forename: Jun-lin
authors.initials: JL
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Tian-lun
authors.initials: TL
authors.lastname: Yang
authors.forename: Han-du
authors.initials: HD
authors.lastname: Deng
authors.forename: Yuan-jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase; D001241:Aspirin