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

Background/AimsCyclooxygenase-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.MethodsSEC 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.ResultsAA 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.ConclusionsAn enhanced production of vasoconstrictor prostanoids, probably PGH2, by SEC contributes to increase vascular tone of cirrhotic livers.