The roles of nitric oxide and prostaglandins in alterations of ulcerogenic and healing responses in adjuvant-induced arthritic rat stomachs.
OBJECTIVE
To examine alterations of gastric ulcerogenic and healing responses in adjuvant-induced arthritic rats.


METHODS
Arthritis was induced in male Dark Agouti rats by injection of Freund's complete adjuvant into the right hind paw.


RESULTS
The gastric ulcerogenic response to indomethacin was markedly increased in AA rats, depending on the degree of arthritic change. By contrast, HCl/ethanol-induced gastric lesions were significantly suppressed in arthritic rats when compared with normal rats. The increased ulcerogenic response to indomethacin was significantly prevented by L-NAME and antineutrophil serum but not by FR167653, while the reduced ulcerogenic response to HCl/ethanol was significantly prevented by L-NAME and partly by indomethacin or NS-398. On the other hand, the healing of chronic gastric ulcers induced by thermal cauterization was also significantly delayed in arthritic rats when compared with normal rats. This delayed healing of gastric ulcers was affected by neither L-NAME, indomethacin nor FR167653. The gastric mucosa of arthritic rats showed a significant increase in both inducible nitric oxide synthase (iNOS) activity and prostaglandin (PG) E2 contents.


CONCLUSIONS
Gastric ulcerogenic and healing responses were altered in arthritic rats. The ulcerogenic response to indomethacin was increased while that to HCl/ethanol was decreased. These changes in ulcerogenic responses may both be accounted for by increased production of NO/iNOS, with the latter also being partially related to elevated production of PGs/COX-2. Moreover, the healing of gastric ulcers was also delayed in arthritic rats, but the mechanism was related to neither NO nor PGs.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan. skato@mb.kyoto-phu.ac.jp
Tanaka
A
A
Kunikata
T
T
Mizoguchi
H
H
Takeuchi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000150:complications* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005620:Freund's Adjuvant; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D013276:Stomach Ulcer / Q000473:pathology / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; D009569:Nitric Oxide; D000431:Ethanol; D005620:Freund's Adjuvant; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D007213:Indomethacin