Experimental and clinical gastrointestinal data reported that NS development involved in impaired epithelial barrier function, altered motility and a lowered threshold to noxious stimuli, but its pathogenesis' role in gastroesophageal reflux disease remains unexplored. Our previous data showed esophagoprotective action of melatonin (MT), due to its vasodilatatory, anti-inflammatory and scavengering activities. We tested the hypothesis that imbalance in production nitrogen active radicals (NAR) may play an important role in the formation of EEB during experimental nonerosive damages during to hypergastrinemia (HG) and hypothyrosis (HT).

Rat groups without/with MT (20mg/kg/day/ip) pretreatment and with induced HG (omeprazol 18 mg/kg/day); HT (merkasolil 16 mg/kg/day/per os) during 28 days and combination with HG+HT were studied. Content of products of plasma NAR was determined by Grease's reagent by generally accepted methods. Histometric analysis (HA) was performed by routine H/E staining method and ultra structural investigation with electronic-microscopy. In the control group NAR concentration was 11.341.41 mkmol/ml; in rats with HG it significally increased to 13.231.41 mkmol/ml (p=0.05); HT – 13.262.07 mkmol/ml and in combination HG+HT for 21% from control group level. HA revealed intercellular changes in EEB during HG, HT and HG+HT and MT attenuated induced esophageal lesions. Tested ASE afforded esophagoprotection against nonerosive EEB damage and this was accompanied by decrease in NAR content. NS plays a critical role in induction of esophageal nonerosive damages, because involves in NO generation due to increases iNOS expression and MT pretreatment weakens signs of NS and can be beneficial in EEB.