title: Protective effects of cariporide on endothelial dysfunction induced by homocysteine.
abstract: OBJECTIVE
  Recent studies have reported that intracellular calcium (Ca(2+)) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na(+)/H(+) exchanger (NHE) is responsible for an increase in the intracellular Ca(2+) concentration in cardiovascular disease. We hypothesized that inhibition of the NHE had protective effects on Hcy-induced endothelial dysfunction.
  
  
  METHODS
  Acetylcholine-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in the rat isolated aorta. The level of reactive oxygen species (ROS) was designed by a specific fluorescent probe. The phosphorylation of the nuclear factor-κB (NF-κB) system was studied by Western blot.
  
  
  RESULTS
  Cariporide significantly prevented Hcy-impaired EDR and increased nitric oxide (NO) release; endothelial NO synthase activity simultaneously decreased ROS production. We also found that cariporide blocked Hcy-induced NF-κB activation and inhibitor-κB degradation, thus inhibiting the production of tumor necrosis factor-α and intercellular adhesion molecule-1.
  
  
  CONCLUSIONS
  The mechanisms of protective effects of cariporide may be related to the inhibition of NHE and the decrease in oxidative stress and inflammatory injury.
authors.affiliation: Department of Pharmacy, Gan Su Province Hospital, Lan Zhou, China.
authors.forename: Shujin
authors.initials: S
authors.lastname: Wu
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Shehua
authors.initials: S
authors.lastname: Yang
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Ge
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology*; D006710:Homocysteine / Q000008:administration & dosage* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C093373:cariporide; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D002118:Calcium