title: Cyclooxygenase-2 and inducible nitric oxide synthase in omental arteries harvested from patients with severe liver diseases: immuno-localization and influence on vascular tone.
abstract: OBJECTIVE
  To investigate the expression of inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) and the role of vasodilatory prostanoids and endogenous nitric oxide (NO) in small omental arteries harvested from patients with severe liver diseases.
  
  
  METHODS
  Ex vivo study of resistance arteries. SETTING. Intensive care unit.
  
  
  METHODS
  Twenty patients undergoing liver transplantation for fulminant hepatic failure (FHF, n=6), cirrhogenous viral hepatitis (CH, n=6) and limited hepatocarcinoma (controls, n=8).
  
  
  METHODS
  Western blot and immunohistochemical labeling for assessment of COX-2 and iNOS expression and localization and ex vivo vascular reactivity studies.
  
  
  RESULTS
  Significant upregulation of COX-2 and iNOS expressions were detected in arteries from FHF and CH patients with a greater increase in the former than in the latter. Ex vivo contractile responses to norepinephrine and the thromboxane A(2) analog, U46619, were not significantly different between patients with severe liver dysfunction and controls. Exposure to either the NO-synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), the cyclooxygenase inhibitor, indomethacin, or their combination did not significantly modify contractions of agonists in controls and CH patients. In FHF, the specific COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (1 micro m/l), but not L-NAME, significantly enhanced the maximal effect ( p<0.01) and the sensitivity ( p<0.01) to norepinephrine.
  
  
  CONCLUSIONS
  COX-2 and iNOS are upregulated in omental arteries from patients with cirrhogenous hepatitis and fulminant hepatic failure. Whereas neither NO nor vasodilatory prostaglandins seem to play a major role in counteracting arterial contractility of arteries from control patients, COX-2 derivatives are involved in lowering the arterial contractility of vessels harvested from FHF patients.
authors.affiliation: Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS (UMR 7034), Illkirch, France.
authors.forename: Antonia
authors.initials: A
authors.lastname: Tabernero
authors.forename: Francis
authors.initials: F
authors.lastname: Schneider
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Potenza
authors.forename: Voahanginirina
authors.initials: V
authors.lastname: Randriamboavonjy
authors.forename: Sylvette
authors.initials: S
authors.lastname: Chasserot
authors.forename: Philippe
authors.initials: P
authors.lastname: Wolf
authors.forename: Delia
authors.initials: D
authors.lastname: Mitolo-Chieppa
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Stoclet
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000328:Adult; D001158:Arteries / Q000201:enzymology* / Q000503:physiopathology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D016022:Case-Control Studies; D051546:Cyclooxygenase 2; D004108:Dilatation, Pathologic; D005260:Female; D006525:Hepatitis, Viral, Human / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D017093:Liver Failure / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D008113:Liver Neoplasms / Q000201:enzymology* / Q000503:physiopathology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009578:Nitrobenzenes / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009852:Omentum / Q000098:blood supply*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000502:physiology*; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin