RGD Reference Report - Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers. - Rat Genome Database

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Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers.

Authors: Gracia-Sancho, J  Lavina, B  Rodriguez-Vilarrupla, A  Garcia-Caldero, H  Bosch, J  Garcia-Pagan, JC 
Citation: Gracia-Sancho J, etal., J Hepatol. 2007 Aug;47(2):220-7. Epub 2007 Apr 5.
RGD ID: 1642445
Pubmed: PMID:17459512   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jhep.2007.03.014   (Journal Full-text)

BACKGROUND/AIMS: Cyclooxygenase-1 (COX-1) is overexpressed in sinusoidal endothelial cells (SEC) of cirrhotic rat livers, and through an enhanced production of vasoconstrictor prostanoids contributes to increase intrahepatic resistance. Our study was aimed at investigating the role of enhanced AA bioavailability modulating the hepatic vascular tone of cirrhotic livers and identifying which prostanoid is involved. METHODS: SEC isolated from control and cirrhotic rat livers were incubated with AA, methoxamine or vehicle. TXA(2) was quantified. In addition, portal perfusion pressure (PP) response curves to AA were performed in rat livers pre-incubated with vehicle, SC-560 (COX-1 inhibitor), Furegrelate (inhibitor of TXA(2) synthesis) and SQ-29548 (PGH(2)/TXA(2) receptor blocker). cPLA2 activity was determined in control and cirrhotic livers. RESULTS: AA and methoxamine incubation promoted a significant increase in TXA(2) release by Cirrhotic-SEC, but not in Control-SEC. AA produced a dose-dependent increase in the PP, associated with increased TXA(2) release. These responses were significantly greater in cirrhotic livers. COX-1 inhibition and PGH(2)/TXA(2) receptor blockade, but not TXA(2) synthase inhibition, markedly attenuated the PP response to AA of cirrhotic livers. Additionally, cirrhotic livers exhibited significantly increased cPLA2 activity. CONCLUSIONS: An enhanced production of vasoconstrictor prostanoids, probably PGH(2), by SEC contributes to increase vascular tone of cirrhotic livers.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PLA2G4AHumanExperimental Liver Cirrhosis  ISOPla2g4a (Rattus norvegicus)protein:increased activity:liverRGD 
Pla2g4aMouseExperimental Liver Cirrhosis  ISOPla2g4a (Rattus norvegicus)protein:increased activity:liverRGD 
Pla2g4aRatExperimental Liver Cirrhosis  IEP protein:increased activity:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pla2g4a  (phospholipase A2 group 4A)

Genes (Mus musculus)
Pla2g4a  (phospholipase A2, group IVA (cytosolic, calcium-dependent))

Genes (Homo sapiens)
PLA2G4A  (phospholipase A2 group IVA)


Additional Information