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

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 (ICA M-1), and a platelet-activating factor (PAF) to the mucosal dysfunction ind uced 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 sam ples were obtained 30 min after terminating the infusion. ET-1 administrati on significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produ ces PMN infiltration and oxidant stress. Blood-to-lumen clearance of Cr-51- EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF an tagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction in duced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation , oxidant stress, and mucosal dysfunction in the rat small intestine and th at ET-1-induced mucosal dysfunction involves a mechanism that includes a ro le for PMNs, ICAM-1, and PAF.