Document Detail


5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes.
MedLine Citation:
PMID:  11832453     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Cysteinyl-leukotrienes (Cys-LTs) increase intrahepatic vascular resistance in normal rat livers. CCl4 cirrhotic rat livers have increased Cys-LT production and 5-lipoxygenase messenger RNA (mRNA) expression. The aim of this study was to investigate the role of 5-lipoxygenase-derived eicosanoids regulating intrahepatic vascular tone in control and CCl4-induced cirrhotic rat livers. METHODS: In different groups of portally perfused control and cirrhotic rat livers, the following were analyzed: a portal perfusion pressure (PP) dose-response curve to LTD4; the effects on PP caused by either vehicle, the selective 5-lipoxygenase inhibitor AA-861, the selective Cys-LT1 receptor antagonist MK-571, or the dual Cys-LT1 and Cys-LT2 receptor antagonist BAY u9773; and immunohistochemistry for 5-lipoxygenase in liver sections of cirrhotic and control livers. RESULTS: Cirrhotic livers have a hyperesponse to LTD4. In control livers, AA-861 and MK-571 produced a moderate and similar reduction in PP. In cirrhotic livers, 5-lipoxygenase inhibition produced a marked and significantly greater reduction in PP than in controls. However, no effect on PP was observed after MK-571 or BAY u9773. 5-Lipoxygenase-positive cells were markedly increased in cirrhotic livers. CONCLUSIONS: Our results suggest that 5-lipoxygenase-derived eicosanoids may contribute to the increased intrahepatic vascular resistance of cirrhotic rat livers and therefore the pathogenesis of portal hypertension.
Authors:
Mariona Graupera; Juan-Carlos Garc?a-Pag?n; Esther Titos; Joan Claria; Anna Massaguer; Jaime Bosch; Juan Rod?s
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gastroenterology     Volume:  122     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-02-08     Completed Date:  2002-03-01     Revised Date:  2010-05-07    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-93     Citation Subset:  AIM; IM    
Affiliation:
Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malaties Digestives Hospital Clinic, University of Barcelona, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonate 5-Lipoxygenase / antagonists & inhibitors*,  metabolism
Benzoquinones / pharmacology
Carbon Tetrachloride
Cysteine / metabolism*
Leukotriene Antagonists / pharmacology
Leukotrienes / metabolism*
Lipoxygenase Inhibitors / pharmacology
Liver Circulation / drug effects,  physiology*
Liver Cirrhosis / chemically induced,  enzymology*
Male
Propionates / pharmacology
Quinolines / pharmacology
Rats
Rats, Wistar
SRS-A / analogs & derivatives*,  pharmacology
Vascular Resistance / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/BAY u9773; 0/Benzoquinones; 0/Leukotriene Antagonists; 0/Leukotrienes; 0/Lipoxygenase Inhibitors; 0/Propionates; 0/Quinolines; 0/SRS-A; 0/cysteinyl-leukotriene; 115104-28-4/verlukast; 52-90-4/Cysteine; 56-23-5/Carbon Tetrachloride; 80809-81-0/2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; EC 1.13.11.34/Arachidonate 5-Lipoxygenase

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