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Am J Physiol Gastrointest Liver Physiol 279: G483-G491, 2000;
0193-1857/00 $5.00
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Vol. 279, Issue 3, G483-G491, September 2000

Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small intestine

Berna K. Oktar1, Tamer Coskun1, Ayhan Bozkurt1, Berrak Ç. Yegen1, Meral Yüksel2, Goncagül Haklar2, Serpil Bilsel2, Fehime Benli Aksungar2, Şule Çetinel3, D. Neil Granger4, and Hizir Kurtel1

Departments of 1 Physiology, 2 Biochemistry, and 3 Histology, Marmara University School of Medicine, 81326 Haydarpasa, İstanbul, Turkey; and 4 Department of Molecular and Cellular Physiology, Louisiana State University, Shreveport, Louisiana 71130

The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of 51Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.

oxidant stress; mucosal permeability; intercellular adhesion molecule-1; platelet-activating factor


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