3-nitrotyrosine and Stomach-Ulcer

It was reported previously that non-steroidal anti-inflammatory drugs (NSAID)-induced gastric damage was markedly aggravated in rats during arthritis, and this response was mediated by the overproduction of nitric oxide (NO) derived from endothelial NO synthase (eNOS) in addition to inducible NO synthase (iNOS). The present study examined the gastric ulcerogenic response to cold-restraint stress in adjuvant arthritic rats, particularly in relation to NO/NOS isozymes. Exposure of normal rats to cold-restraint stress (13 degrees C) produced slight gastric damage 3 h later, but the ulcerogenic response was markedly aggravated in arthritic rats. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (a nonselective inhibitor of NOS) slightly increased the cold-restraint stress-induced gastric lesions in normal rats, but dose-dependently prevented the aggravation of these lesions in arthritic rats. The increased ulcerogenic response in arthritic rats was significantly suppressed by 1400 W (a selective inhibitor of iNOS) and L-iminoethyl ornithine (L-NIO) (a selective inhibitor of eNOS), but not by N(G)-propyl-L-arginine (L-NPA) (a selective inhibitor of nNOS), and almost totally abolished by the co-administration of 1400 W and L-NIO. The mucosal expression levels of eNOS and iNOS but not nNOS mRNAs were enhanced in arthritic rats compared with normal rats. The aggravation of stress-induced gastric lesions in arthritic rats was also significantly suppressed by pretreatment with glutathione. These results suggest that the gastric ulcerogenic response to cold-restraint stress is enhanced in arthritic rats, similar to that induced by NSAIDs, and this phenomenon may be causally associated with the upregulation of eNOS/NO in addition to iNOS/NO.

Topics: Animals; Arthritis, Experimental; Blotting, Western; Cold Temperature; Enzyme Inhibitors; Gastric Mucosa; Glutathione; Guanidines; Immunohistochemistry; Isoenzymes; Male; Mycobacterium tuberculosis; NG-Nitroarginine Methyl Ester; Nitric Oxide Donors; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Restraint, Physical; Stomach Ulcer; Stress, Psychological; Tyrosine