Abstract Title:

Role of endothelial nitric oxide synthase in aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats.

Abstract Source:

J Physiol Pharmacol. 2009 Dec;60(4):147-55. PMID: 20065509

Abstract Author(s):

S Kato, F Ohkawa, Y Ito, K Amagase, K Takeuchi

Article Affiliation:

Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan. skato@mb.kyoto-phu.ac.jp


The role of nitric oxide synthase (NOS) isozymes in the aggravation of indomethacin-induced gastric damage in adjuvant arthritic rats was investigated. Two weeks after injection of Freund's complete adjuvant, the animals were given indomethacin, and the stomach was examined for damage 4 h later. Indomethacin caused hemorrhagic lesions in the normal rat stomach, and these lesions were markedly aggravated in arthritic rats. Pretreatment with L-NAME (a nonselective inhibitor of NOS) and aminoguanidine (a relative selective inhibitor of iNOS) did not affect the ulcerogenic response in normal rats but dose-dependently prevented the aggravation of lesions in arthritic rats, but the effect of aminoguanidine was apparently less than that of L-NAME. The increased ulcerogenic response in arthritic rats was significantly suppressed by 1400 W (a selective inhibitor of iNOS) and L-NIO (a selective inhibitor of eNOS) but not by L-NPA (a selective inhibitor of nNOS). The concurrent administration of 1400 W and L-NIO almost totally abolished the aggravation of damage in arthritic rats. The expressions of eNOS and iNOS but not nNOS in the gastric mucosa were clearly enhanced in arthritic rats. Mucosal levels of non-protein sulfhydryls were significantly lower in arthritic rats than those in normal rats. The aggravation of damage in arthritic rats was significantly prevented by glutathione. These results suggest that the increased ulcerogenic response to indomethacin in arthritic rat stomachs is mediated by NO derived from eNOS in addition to iNOS. It is assumed that eNOS/NO may act harmfully on the gastric mucosa of arthritic rats with mucosal SH deficiency.

Study Type : Animal Study
Additional Links
Adverse Pharmacological Actions : Inflammatory : CK(423) : AC(132)

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