Document Detail


Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension.
MedLine Citation:
PMID:  18457899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Splanchnic vasodilation initiates the hyperdynamic syndrome in portal hypertension. We aimed to explore molecular mechanisms involved in the development of mesenteric vasodilation in portal hypertension. METHODS: Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models. RESULTS: Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively. CONCLUSIONS: Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.
Authors:
Mar Coll; Joan Genescà; Imma Raurell; Aina Rodríguez-Vilarrupla; Marc Mejías; Teresa Otero; Marc Oria; Rafael Esteban; Jaime Guardia; Jaime Bosch; María Martell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-18
Journal Detail:
Title:  Journal of hepatology     Volume:  49     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-10     Completed Date:  2008-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  43-51     Citation Subset:  IM    
Affiliation:
Liver Diseases Laboratory, Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-127, 08035 Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carbon Tetrachloride / toxicity
Disease Models, Animal
Dopamine beta-Hydroxylase / genetics,  metabolism
Down-Regulation / genetics
Gene Expression Profiling*
Hypertension, Portal / chemically induced,  genetics*,  physiopathology*
Immunohistochemistry
Ligation
Liver Cirrhosis / chemically induced,  genetics,  physiopathology
Male
Mesenteric Artery, Superior / physiology
Norepinephrine / physiology*
Oligonucleotide Array Sequence Analysis
Portal Vein
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Splanchnic Circulation / physiology*
Synaptosomal-Associated Protein 25 / genetics,  metabolism
Tyrosine 3-Monooxygenase / genetics,  metabolism
Vasodilation / physiology*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Snap25 protein, rat; 0/Synaptosomal-Associated Protein 25; 51-41-2/Norepinephrine; 56-23-5/Carbon Tetrachloride; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 1.14.17.1/Dopamine beta-Hydroxylase

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