Endogenous bacteria-triggered inducible nitric oxide synthase activation protects the ovariectomized rat stomach.
Under experimental circumstances, ovariectomy attenuates gastric mucosal injury where nitric oxide (NO)-mediated pathways are involved. In this study, we have examined the changes in constitutive (cNOS) and inducible NO synthase (iNOS) enzyme activities (assessed by the citrulline assay), and the role of endogenous bacteria in ovariectomy-provoked mucosal defence. Gastric lesions were induced by indomethacin (50 mg/kg, s.c.) over a 4 h period in sham-operated and ovariectomized female Wistar rats. Groups of animals received the wide-spectrum antibiotic ampicillin (800 mg/kg/day, p.o., for 3 days), 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 decreased cNOS activity (resulting an elevated total gastric NOS level), and protected the stomach, effects reversed by ampicillin treatment. In ovary-intact rats, administration of bacterial endotoxin enhanced gastric iNOS activity and reduced lesion-formation. These results suggest that ovariectomy improves gastric mucosal defence perhaps by endogenous bacteria-triggered induction of iNOS.
Morschl
E
E
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Pávó
I
I
Varga
G
G
Nemcsik
J
J
László
F
F
Whittle
B J
BJ
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D018407:Bacterial Physiological Phenomena; D019610:Cytoprotection / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology; D004789:Enzyme Activation / Q000502:physiology*; D004926:Escherichia coli; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D010406:Penicillins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004731:Endotoxins; D010406:Penicillins; D000667:Ampicillin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat