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(Circulation. 2003;107:1407.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Cyclooxygenase-2 Expression and Role of Vasoconstrictor Prostanoids in Small Mesenteric Arteries From Patients With Crohn’s Disease

Antonia Tabernero, PhD; Jean-Marie Reimund, MD, PhD; Sylvette Chasserot, PhD; Christian Dominique Muller, PhD; Ramaroson Andriantsitohaina, PhD

From Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Illkirch, France (A.T., C.D.M., R.A.); Hépato-Gastroentérologie et d’Assistance Nutritive, HUS, Hôpital de Hautepierre, Strasbourg, France (J.-M.R.); and CNRS UPR 2356, Strasbourg, France (S.C.).

Correspondence to Ramaroson Andriantsitohaina, PhD, Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR-CNRS 7034, 74 route du Rhin, 67401 Illkirch, France. E-mail nain{at}aspirine.u-strasbg.fr

Background— The present study investigates the vascular reactivity and the involvement of nitric oxide and prostanoids in regulating vasoconstriction of small mesenteric arteries from patients with Crohn’s disease (CD) to understand the vascular component of this pathology.

Methods and Results— An increased production of proinflammatory cytokines (tumor necrosis factor- and interleukins 1ß, 6, and 8) has been observed in biopsy specimens of inflammatory intestinal mucosa. However, contractile responses of small mesenteric arteries from CD patients in response to norepinephrine were not changed ex vivo when compared with controls. Exposure to either the nitric oxide synthase inhibitor N^G-nitro-L-arginine or the cyclooxygenase (COX) inhibitor indomethacin did not modify contractions induced by norepinephrine in either control or CD patients. However, in the latter, the specific COX-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide significantly attenuated norepinephrine-induced vasoconstriction. Furthermore, immunohistochemical analysis showed marked COX-2 expression in the whole arterial wall of vessels from CD patients. Vessels from control patients exhibited weak COX-2 staining in the adventitial and endothelial layers only.

Conclusions— The above results provide direct evidence for COX-2 expression in small mesenteric arteries from CD patients. They also shed new light on the involvement of vasoconstrictor metabolites of COX in regulating contraction of these arteries. Of particular interest is the balance between vasoconstrictor products from COX-2 and unidentified vasodilatory products that maintained vascular reactivity in a physiological range despite an increase of circulatory cytokines in patients with CD.

Key Words: arteries • inflammation • nitric oxide • prostaglandins • Crohn’s disease

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