RGD Reference Report - 5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes. - Rat Genome Database

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5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes.

Authors: Graupera, M  Garcia-Pagan, JC  Titos, E  Claria, J  Massaguer, A  Bosch, J  Rodes, J 
Citation: Graupera M, etal., Gastroenterology. 2002 Feb;122(2):387-93.
RGD ID: 1626153
Pubmed: PMID:11832453   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
portal hypertension  ISOAlox5 (Rattus norvegicus)1626153; 1626153associated with Liver Cirrhosis and ExperimentalRGD 
portal hypertension  IDA 1626153associated with Liver Cirrhosis and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Mus musculus)
Alox5  (arachidonate 5-lipoxygenase)

Genes (Homo sapiens)
ALOX5  (arachidonate 5-lipoxygenase)


Additional Information