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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Jan;114(1):8–12. doi: 10.1111/j.1476-5381.1995.tb14898.x

Endotoxin inhibition of distension-stimulated gastric acid secretion in rat: mediation by NO in the central nervous system.

M D Barrachina 1, B J Whittle 1, S Moncada 1, J V Esplugues 1
PMCID: PMC1510176  PMID: 7712033

Abstract

1. The involvement of nitric oxide in the acute inhibitory effects of low doses of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.) administration, on gastric acid secretion stimulated by distension or i.v. infusion of pentagastrin has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric distension (20 cm water intragastric pressure) within 30 min of administration. 3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administration of endotoxin (800 ng kg-1). 4. Prior i.c.v. administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 800 micrograms kg-1) restored the acid secretory responses to distension in rats treated with endotoxin (i.c.v.). 5. Likewise, i.v. administration of endotoxin (5 micrograms kg-1) abolished the acid secretory response induced by gastric distension within 30 min of administration. Prior i.c.v. injection of L-NAME (800 micrograms kg-1) or its i.v. administration (10 mg kg-1) restored acid secretory responses in rats receiving i.v. endotoxin. 6. The reversal by L-NAME (i.v.) of the acid inhibitory effects of endotoxin (i.v.) was prevented by L-arginine (12 mg kg-1, i.c.v. or 100 mg kg-1, i.v.), but not by its enantiomer D-arginine. 7. The present results imply the existence of an acute response to endotoxin involving NO synthesis in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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