Changes in gastric mucosal ulcerogenic responses in rats with adjuvant arthritis: role of nitric oxide.
OBJECTIVE
To examine gastric mucosal ulcerogenic responses to indomethacin and HCl/ethanol in adjuvant arthritic (AA) rats.


RESULTS
Arthritis was induced in male Dark Agouti (DA) rats by injection of Freund's complete adjuvant (FCA) into the right hind paw. The gastric ulcerogenic response to indomethacin was markedly worsened in AA rats, depending on the degree of arthritic change. This aggravation of indomethacin-induced gastric lesions in AA rats was significantly prevented by NG-nitro-L-arginine methyl ester (L-NAME) and amino-guanidine as well as dexamethasone. In contrast, the mucosal ulcerogenic response to HCl/ethanol was inhibited in AA rats. The suppression of HCl/ethanol-induced gastric lesions in AA rats was reversed almost totally by L-NAME and aminoguanidine as well as dexamethasone and partly by indomethacin. The expression of inducible nitric oxide synthase (iNOS) mRNA was observed in the stomach of AA rats but not of normal rats. Moreover, the luminal releases of nitric oxide (NO) metabolites as well as prostaglandin (PG) E2 were significantly increased in AA rats.


CONCLUSIONS
The gastric mucosal ulcerogenic responses were modified in AA rats, in different manners depending on the irritants; an increase in response to indomethacin and a decrease in response to HCl/ethanol. These changes may both be accounted for by increased production of NO by iNOS, and the latter is also partly related to increased production of PGs.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan. skato@mb.kyoto-phu.ac.jp
Tanaka
A
A
Kunikata
T
T
Nishijima
M
M
Takeuchi
K
K
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001835:Body Weight; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced*
D012333:RNA, Messenger; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D015232:Dinoprostone; D007213:Indomethacin