Roles of inducible nitric oxide synthase in the development and healing of experimentally induced gastric ulcers.

The roles of inducible nitric oxide synthase (iNOS) in the development and healing of gastric ulcers have not been fully characterized. We characterized iNOS expression in experimentally induced ulcers in rat and mouse stomachs and investigated the roles of iNOS using iNOS gene-deficient (iNOS-/-) mice and wildtype mice. Gastric ulcers were induced in rats and mice by the application of acetic acid and cryoinjury, respectively. iNOS expression was detected on days 1-7 and peaked 3 days after ulcer induction in the rat. iNOS-positive cells were distributed mainly among the infiltrating cells and fibroblasts in the ulcer bed. The almost similar courses of healing and iNOS expression were observed in the ulcers of mice. During the course of healing, the iNOS gene status did not affect cell proliferation in the healing zone or vessel formation in the ulcer bed. iNOS deficiency, however, caused larger ulcers and severer inflammation during ulcer healing; the clearance of inflammatory cells in the ulcer bed by apoptosis was also delayed when the ulcer was re-epithelialized in the iNOS-deficient mice. These results indicate that iNOS is expressed in the ulcer bed and that iNOS activity may play beneficial roles in the ulcer repair process, possibly by regulating inflammation.