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 inducible NO synthase (iNOS) activities with the development of gastric mucosal lesions induced by water immersion restraint (WIR) stress were investigated in rats pretreated with and without NOS inhibitors. A decrease in cNOS activity and an increase in iNOS activity in the gastric mucosa occurred with gastric mucosal lesion development. Pretreatment with N(G)-monomethyl L-arginine, a non-selective NOS inhibitor, enhanced gastric mucosal lesion development with inhibition of gastric mucosal cNOS and iNOS activities, although the inhibited iNOS activity was still higher than the normal level. Pretreatment with aminoguanidine, a selective iNOS inhibitor, prevented gastric mucosal lesion development with 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 gastric mucosa are closely related to the development of gastric mucosal lesions.