Abstract | BACKGROUND & AIMS: Arterial vasodilation plays a role in the pathogenesis of the complications of cirrhosis. This vasodilation is caused by the overproduction of arterial nitric oxide (NO). Bacterial translocation may be involved in NO synthase (NOS) up-regulation by activating both endothelial NOS (eNOS) and inducible NOS (iNOS). The prevention of intestinal gram-negative translocation by norfloxacin administration corrects systemic circulatory changes by decreasing NO production in cirrhosis. However, the signaling mechanisms for NO overproduction from bacterial translocation are unknown. In this study, we investigated the signal transduction pathway of bacterial translocation-induced aortic NOS up-regulation in cirrhotic rats. METHODS: Proinflammatory cytokine levels, Akt and NOS activities, eNOS phosphorylation, and NOS expressions were assessed in aorta from norfloxacin-treated and untreated cirrhotic rats. Norfloxacin was administered to reduce intestinal bacterial translocation. RESULTS: CONCLUSIONS: This study identifies a signaling pathway in which bacterial translocation induces aortic NOS up-regulation and thus NO overproduction in cirrhotic rats. These results strongly suggest that bacterial translocation and proinflammatory cytokines play a role in systemic NO overproduction in cirrhosis by the Akt pathway.
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Authors | Khalid A Tazi, Richard Moreau, Philippe Hervé, Agnes Dauvergne, Dominique Cazals-Hatem, Frederic Bert, Odile Poirel, Anne Rabiller, Didier Lebrec |
Journal | Gastroenterology
(Gastroenterology)
Vol. 129
Issue 1
Pg. 303-14
(Jul 2005)
ISSN: 0016-5085 [Print] United States |
PMID | 16012955
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Proto-Oncogene Proteins
- Tumor Necrosis Factor-alpha
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Nos2 protein, rat
- Nos3 protein, rat
- Transaminases
- Akt1 protein, rat
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
- Norfloxacin
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Topics |
- Animals
- Aorta
(drug effects, enzymology, immunology)
- Bacterial Translocation
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Feces
(microbiology)
- Liver Cirrhosis
(immunology, metabolism, pathology)
- Male
- Nitric Oxide Synthase
(metabolism)
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Norfloxacin
(pharmacology)
- Phosphorylation
- Protein Serine-Threonine Kinases
(metabolism)
- Proto-Oncogene Proteins
(metabolism)
- Proto-Oncogene Proteins c-akt
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects, physiology)
- Transaminases
(blood)
- Tumor Necrosis Factor-alpha
(immunology, metabolism)
- Up-Regulation
(drug effects)
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