Shibamoto Toshishige, Kamikado Chiaki, Koyama Shozo
Department of Physiology II, Kanazawa Medical University, Uchinada, Japan.
Pflugers Arch. 2008 Jun;456(3):467-77. doi: 10.1007/s00424-007-0437-6. Epub 2008 Jan 5.
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.
在肝硬化中，肝内血管阻力增加的定位以及肝段血管对内皮素-1的反应尚不清楚。我们测定了孤立门静脉灌注胆管结扎（BDL）诱导的肝硬化大鼠肝脏的肝段血管阻力及其对内皮素-1的反应。通过分析在同时阻断流入和流出灌注线的双重阻断操作期间门静脉（Ppv）和肝静脉（Phv）压力的曲线来获得门静脉阻断压力（Ppo）和肝静脉阻断压力（Phvo）。根据Ppv、Ppo、Phvo和Phv之间的压力梯度，将门静脉-肝静脉阻力分为门静脉的三个节段[Rpv =（Ppv - Ppo）/血流量（Q）]、肝血窦[Rsinus =（Ppo - Phvo）/Q]和肝静脉[Rhv =（Phvo - Phv）/Q]阻力。BDL组肝脏的Rsinus显著高于假手术组，而Rpv或Rhv则无显著差异。在假手术组和BDL组中，内皮素-1（0.1 - 1 nM）使Rpv和Rsinus增加的幅度相似，但不影响Rhv。在3 nM时，BDL组肝脏中Rpv的反应性低于假手术组，但Rsinus的反应性在BDL组和假手术组之间相似。总之，肝血窦阻力增加是BDL诱导的肝硬化肝内阻力增加的原因。在假手术组和肝硬化肝脏中，内皮素-1使门静脉和肝血窦收缩，但不使肝静脉收缩。肝硬化肝脏中肝血窦对内皮素-1的收缩性未受损。
