DETERMINATION OF ENDOGENOUSLY PRODUCED NITRIC OXIDE (NO) IN RAT STOMACH : CYTOPROTECTIVE ROLE OF NO

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Nitric oxide (NO) is biologically synthesized in stomach by three forms of nitric oxide synthase (NOS). Nitrite in saliva derived from dietary nitrate is chemically reduced to NO under the acidic conditions in the stomach. Thus, gastrointestinal tracts are highly exposed to NO derived from both endogenous and exogenous origins. Recently, endogenously synthesized NO in stomach has been demonstrated to exert physiological and pathophysiological effects on gastric mucosal blood flow, acid and mucus secretion, gastric motility, and regulates mucosal defense and injury. In this study we investigated the roles of NO on ethanol-induced gastric mucosal injury in rats. Under urethane anesthesia, a rat stomach was mounted on an ex vivo chamber ; saline and then aqueous ethanol (43%) solutions were perfused. NO production in stomach tissues was analyzed by spin trapping technique combined with electron paramagnetic resonance spectroscopy. Nitrite and nitrate (NOx) in the luminal fluid were determined by the Griess-reaction assay with HPLC.Gastric mucosal blood flow, luminal pH, gastric mucosal potential difference, and area of the macroscopic mucosal injury were evaluated with/without preadministration of NOS inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME). Preadministration of L-NAME aggravated mucosal damage and suppressed increase of mucosal blood flow. In conclusion, endogenously produced NO plays an important role in the protection against ethanol-induced gastric injury via regulation of gastric mucosal blood flow. Further, we investigated the physiological activities and in vivo distribution of dinitrosyl dithiolato iron complex (DNIC), which has been recognized as one of endogenous NO donor molecules. A combination of ex vivo and in vivo EPR spectrometry made it possible to reveal that DNIC not only possesses an excellent membrane-permeability but also has a markedly high affinity for the liver and kidney.