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Nitrergic modulation of gastrointestinal function during early endotoxemia.

Authors
  • Quintana, E1
  • Barrachina, M D
  • Esplugues, J V
  • 1 Department of Pharmacology, Faculty of Medicine, University of Valencia, Avd. Blasco Ibáñez 15, 46010 Valencia, Spain. , (Spain)
Type
Published Article
Journal
Current pharmaceutical design
Publication Date
Jan 01, 2006
Volume
12
Issue
34
Pages
4525–4535
Identifiers
PMID: 17168758
Source
Medline
License
Unknown

Abstract

After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the challenge and restore homeostasis. Systemic administration of low doses of endotoxin (5-40 microg/kg) to rats is associated with changes in gastrointestinal motor function, inhibition of gastric acid secretion and increase in the gastric mucosal resistance to damage. These changes are rapid in onset (observed within one hour), not related to vascular dysfunction, and appear to be mediated by mechanisms that involve the peripheral and the central nervous system. Nitric oxide (NO) plays a central role in the physiology of the gastrointestinal tract and its response to illness. Accumulated evidence supports an increase of NO synthesis in the brainstem, as well as in the gastric myenteric plexus thirty minutes after endotoxin administration. Such a synthesis is due to constitutive nitric oxide synthase (NOS) and occurs before the induction of NOS takes place. In this review we provide experimental evidence supporting the hypothesis that activation of a physiologic mechanism, mediated by the autonomic and the central nervous systems as well as constitutive NOS isoforms, is involved in acute changes of gastrointestinal function during early endotoxemia.

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