Cyclooxygenase-2 and inducible nitric oxide synthase in omental arteries harvested from patients with severe liver diseases: immuno-localization and influence on vascular tone

Byline: Antonia Tabernero (1), Francis Schneider (2), Maria Assunta Potenza (3), Voahanginirina Fidi-soa Randriamboavonjy (1), Sylvette Chasserot (4), Philippe Wolf (5), Delia Mitolo-Chieppa (3), Jean-Claude Stoclet (1), Ramaroson Andriantsitohaina (1) Keywords: Artery, resistance Cyclooxygenase Human Liver failure, acute Liver, diseases Nitric oxide Vasoconstriction 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. Design. Ex vivo study of resistance arteries. Setting. Intensive care unit. Patients. Twenty patients undergoing liver transplantation for fulminant hepatic failure (FHF, n=6), cirrhogenous viral hepatitis (CH, n=6) and limited hepatocarcinoma (controls, n=8). Interventions. Western blot and immunohistochemical labeling for assessment of COX-2 and iNOS expression and localization and ex vivo vascular reactivity studies. Measurements and 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.sub.2 analog, U46619, were not significantly different between patients with severe liver dysfunction and controls. Exposure to either the NO-synthase inhibitor, N.sup.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 Aum/l), but not L-NAME, significantly enhanced the maximal effect (p 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. Author Affiliation: (1) Laboratoire de Pharmacologie et Physicochimie des Interactions Cellulaires et Moleculaires, CNRS (UMR 7034), Illkirch, France (2) Service de Reanimation Medicale, Centre Hospitalier Universitaire de Hautepierre, Avenue Moliere, 67098, Strasbourg, France (3) Institute of Pharmacology, Medical School, University of Bari, Bari, Italy (4) , CNRS UPR 2356, Strasbourg, France (5) Service de Transplantation, Centre Hospitalier Universitaire de Hautepierre, Strasbourg, France Article History: Received Date: 04/06/2002 Accepted Date: 21/11/2002 Article note: Electronic Publication