NITRIC-OXIDE AND SENSORY AFFERENT NEURONS MODULATE THE PROTECTIVE EFFECTS OF LOW-DOSE ENDOTOXIN ON RAT GASTRIC-MUCOSAL DAMAGE

Pretreatment (1 h) with low doses (5-40 mu g/kg i.p.) of Escherichia coli endotoxin dose dependently reduced the gastric mucosal damage induced by a 10 min challenge with 1 ml ethanol (50% and 100%) in conscious rats. Treatment with the nitric oxide synthesis inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40 mu g/kg i.p.). The actions of L-NAME were reversed by the prior administration of L-arginine (100 mg/kg i.p.). The protective effects of endotoxin were not influenced by pretreatment with dexamethasone (5 mg/kg s.c, twice) or indomethacin (5 mg/kg s.c.). However, ablation of sensory afferent neurones by capsaicin pretreatment (20, 30 and 50 mg/kg s.c.) abolished the mucosa protective effects of endotoxin (40 mu g/kg). These findings suggest that the protection elicited by low doses of endotoxin against ethanol-induced mucosal damage involves synthesis of nitric oxide and activation of sensory neurones.