Cyclooxygenase-2 expression and role of vasoconstrictor prostanoids in small mesenteric arteries from patients with Crohn's disease.
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.


RESULTS
An increased production of proinflammatory cytokines (tumor necrosis factor-alpha and interleukins 1beta, 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.
Tabernero
Antonia
A
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Illkirch, France.
Reimund
Jean-Marie
JM
Chasserot
Sylvette
S
Muller
Christian Dominique
CD
Andriantsitohaina
Ramaroson
R
D000328:Adult; D003424:Crohn Disease / Q000201:enzymology* / Q000503:physiopathology*; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000201:enzymology* / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D014661:Vasoconstriction
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; 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