| 5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes. | |
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MedLine Citation:
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PMID: 11832453 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Gastroenterology Volume: 122 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 2002 Feb |
Date Detail:
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Created Date: 2002-02-08 Completed Date: 2002-03-01 Revised Date: 2010-05-07 |
Medline Journal Info:
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Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
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Languages: eng Pagination: 387-93 Citation Subset: AIM; IM |
Affiliation:
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Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malaties Digestives Hospital Clinic, University of Barcelona, Barcelona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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