Endogenous bacteria-triggered inducible nitric oxide synthase activation protects the ovariectomized rat stomach

Under experimental circumstances, ovariectomy attenuates gastric mucosal in jury where nitric oxide (NO)-mediated pathways are involved. In this study, we have examined the changes in constitutive (cNOS) and inducible NO synth ase (iNOS) enzyme activities (assessed by the citrulline assay), and the ro le of endogenous bacteria in overiectomy-provoked mucosal defence. Gastric lesions were induced by indomethacin (50 mg/kg, s.c.) over a 4 h period in sham-operated and ovariectornized female Wistar rats. Groups of animals rec eived the wide-spectrum antibiotic ampicillin (800 mg/kg/day, p.o., for 3 d ays), and others were injected with bacterial endotoxin (E. coli, 3 mg/kg, i.v., 5 h before autopsy). We found that ovariectomy increased iNOS and dec reased cNOS activity (resulting an elevated total gastric NOS level), and p rotected the stomach, effects reversed by ampicillin treatment. In ovary-in tact rats, administration of bacterial endotoxin enhanced gastric iNOS acti vity and reduced lesion-formation. These results suggest that ovariectomy i mproves gastric mucosal defence perhaps by endogenous bacteria-triggered in duction of iNOS. (C) 2001 Elsevier Science Ltd. All rights reserved.