Journal of Hepatology
Volume 47, Issue 2 , Pages 220-227, August 2007

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

Hepatic Hemodynamic Laboratory, Liver Unit, IMDIM, Hospital Clínic, Ciberehd and Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036 Barcelona, Spain

Received 28 November 2006; received in revised form 14 February 2007; accepted 3 March 2007. published online 05 April 2007.

Abstract 

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. TXA2 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 TXA2 synthesis) and SQ-29548 (PGH2/TXA2 receptor blocker). cPLA2 activity was determined in control and cirrhotic livers.

Results

AA and methoxamine incubation promoted a significant increase in TXA2 release by Cirrhotic-SEC, but not in Control-SEC. AA produced a dose-dependent increase in the PP, associated with increased TXA2 release. These responses were significantly greater in cirrhotic livers. COX-1 inhibition and PGH2/TXA2 receptor blockade, but not TXA2 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 PGH2, by SEC contributes to increase vascular tone of cirrhotic livers.

Keywords: Intrahepatic resistance, Phospholipase A2, Sinusoidal endothelial cells, Arachidonic acid, PGH2

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☆ The authors who have taken part in this study declared that they have no relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research. They did not receive funding from the manufacturers to carry out this study.

PII: S0168-8278(07)00191-2

doi:10.1016/j.jhep.2007.03.014

Journal of Hepatology
Volume 47, Issue 2 , Pages 220-227, August 2007

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