Increased sinusoidal resistance is responsible for the basal state and endothelin-induced venoconstriction in perfused cirrhotic rat liver.

The localization of increased intrahepatic vascular resistance and the segmental vascular responsiveness to endothelin-1 are not well known in liver cirrhosis. We determined the segmental vascular resistances and their response to endothelin-1 of isolated portally perfused bile duct ligation (BDL)-induced cirrhotic rat livers. The portal occlusion pressure (Ppo) and the hepatic venous occlusion pressure (Phvo) were obtained by analyzing the profiles of the portal (Ppv) and hepatic venous (Phv) pressures during the double occlusion maneuver of simultaneous occlusions of the inflow and outflow perfusion lines. From the pressure gradients among Ppv, Ppo, Phvo, and Phv, the portal-hepatic venous resistance was assigned to three segments of the portal [Rpv = (Ppv - Ppo)/blood flow (Q)], sinusoidal [Rsinus = (Ppo - Phvo)/Q] and hepatic venous [Rhv = (Phvo - Phv)/Q] resistances. Rsinus, but not Rpv or Rhv, was significantly greater in BDL livers than in sham livers. Endothelin-1 (0.1-1 nM) increased Rpv and Rsinus to a similar magnitude, but not Rhv, in both sham and BDL. At 3 nM, the responsiveness of Rpv was smaller in BDL than in sham, but that of Rsinus were similar between in BDL and sham. In conclusion, increased sinusoidal resistance accounts for increased intrahepatic resistance of BDL-induced liver cirrhosis. Endothelin-1 contracts portal veins and sinusoids, but not hepatic veins, in both sham and cirrhotic livers. Sinusoidal contractility to endothelin-1 is not impaired in cirrhotic livers.