| Abstrakt: |
Objective: The correlation between mucosal generation of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastric adaptive cytoprotection was investigated.¶ Materials and Treatment: Male Sprague-Dawley rats were pretreated with either Nw-nitro-L-arginine methyl ester (L-NAME, 12.5mg/kg i.v.) or indomethacin (5mg/kg s.c.). Following that, mild irritant 20% ethanol was administered, 15min prior to 100% ethanol challenge.¶ Methods: Macroscopic gastric mucosal damage, NO synthase activity, mucosal PGE2 and leukotriene C4 (LTC4) levels were measured.¶ Results: Administration of L-NAME and indomethacin significantly reduced the protective action of 20% ethanol against 100% ethanol-induced gastric mucosal damage. Besides, mucosal activity of constitutive NO (cNO) synthase, but not of the inducible isozyme (iNO synthase), was elevated following 20% ethanol treatment. This was accompanied by a reduction in mucosal leukotriene C4 level. Indomethacin significantly inhibited mucosal PGE2 biosynthesis but increased cNO synthase activity. Nevertheless, L-NAME reduced both cNO and iNO formation and prevented the increase in cNO formation caused by 20% ethanol, while enhancing mucosal PGE2 production. Combined L-NAME and indomethacin treatment markedly potentiated ethanol-induced mucosal damage, and completely prevented the increase in cNO or PGE2 biosynthesis when either compound was given alone.¶ Conclusions: These findings suggest a co-regulatory relationship between mucosal NO and PG in the gastric defense system, which will be released after activation by the mild irritants to induce cytoprotection. [ABSTRACT FROM AUTHOR] |
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