Cyclooxygenase-2 and inducible nitric oxide synthase in omental arteries harvested from patients with severe liver diseases: immuno-localization and influence on vascular tone.
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.
Tabernero
Antonia
A
Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS (UMR 7034), Illkirch, France.
Schneider
Francis
F
Potenza
Maria Assunta
MA
Randriamboavonjy
Voahanginirina
V
Chasserot
Sylvette
S
Wolf
Philippe
P
Mitolo-Chieppa
Delia
D
Stoclet
Jean-Claude
JC
Andriantsitohaina
Ramaroson
R
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
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