ROLE OF GASTRIC-MUCOSAL CONSTITUTIVE AND INDUCIBLE NITRIC-OXIDE SYNTHASES IN THE DEVELOPMENT OF STRESS-INDUCED GASTRIC-MUCOSAL LESIONS IN RATS

Changes in gastric mucosal constitutive NO synthase (cNOS) and inducib le NO synthase (iNOS) activities with the development of gastric mucos al lesions induced by water immersion restraint (WIR) stress were inve stigated in rats pretreated with and without NOS inhibitors. A decreas e in cNOS activity and an increase in iNOS activity in the gastric muc osa occurred with gastric mucosal lesion development. Pretreatment wit h N-G-monomethyl L-arginine, a non-selective NOS inhibitor, enhanced g astric mucosal lesion development with inhibition of gastric mucosal c NOS and NOS activities, although the inhibited iNOS activity was still higher than the normal level. Pretreatment with aminoguanidine, a sel ective iNOS inhibitor, prevented gastric mucosal lesion development wi th inhibition of iNOS activity and maintenance of cNOS activity in the gastric mucosa. These results indicate that in WIR-stressed rats, an increase in iNOS activity and a decrease in cNOS activity in the gastr ic mucosa are closely related to the development of gastric mucosal le sions. (C) 1997 Academic Press.