Involvement of Nitric Oxide in Lipopolysaccharide-Induced Gastric Relaxation in Mice

Abstract

The effects of nitric oxide synthase (NOS) inhibitors aminoguanidine (AG), S-methylisothiourea (SMT), Ν w -nitro-L-arginine methyl ester (L-NAME), and dexamethasone (DEX) on blood and gastric tissue concentrations of nitrite and nitrate and stomach size were investigated. Experiments were performed on mice in the physiological state and on endotoxemic mice that received E. coli 0111: B4 lipopolysaccharide (LPS). LPS induced a dose-dependent increase in nitrate concentrations in blood plasma, gastric corpus, and fundus. LPS did not affect nitrite concentration in the gastric fundus. NOS inhibitors decreased the nitrate level in blood serum in LPS-induced endotoxemia. In gastric corpus L-NAME and DEX effectively decreased the LPS-induced nitrate level, while in gastric fundus, L-NAME, SMT, and DEX were effective. AG was not effective in either gastric corpus or fundus. LPS induced a non-dose-dependent relaxation of stomach that could not be reversed either by treatment with NOS inhibitors or DEX. In conclusion, both inducible and constitutive isoforms of NOS are involved in NO production in inflammatory conditions, and the relaxation of whole stomach is not related to NO production. However, it is possible that the local production of NO may be involved in LPS-induced fundus relaxation.