Nitric oxide and sensory afferent neurones modulate the protective effects of low-dose endotoxin on rat gastric mucosal damage.
Pretreatment (1 h) with low doses (5-40 micrograms/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, NG-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40 micrograms/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 neurons by capsaicin pretreatment (20, 30 and 50 mg/kg s.c.) abolished the mucosa protective effects of endotoxin (40 micrograms/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.
Barrachina
D
D
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Calatayud
S
S
Moreno
L
L
Martínez-Cuesta
A
A
Whittle
B J
BJ
Esplugues
J V
JV
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D004791:Enzyme Inhibitors; D000431:Ethanol; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin