Watanabe Norihito, Takashimizu Shinji, Nishizaki Yasuhiro, Kojima Seiichiro, Kagawa Tatehiro, Matsuzaki Shohei
Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Bohseidai, Isehara, 259-1193, Japan.
J Gastroenterol. 2007 Sep;42(9):775-82. doi: 10.1007/s00535-007-2093-1. Epub 2007 Sep 25.
Sinusoidal endothelial fenestrae (SEF) regulate the sinusoidal circulation by altering their diameter and number. This study documented the effects of endothelin (ET) receptor antagonists on SEF and hepatic microcirculation.
The portal pressure and hepatic tissue blood flow were measured with a hydromanometer and a laser Doppler blood flow meter, respectively. BQ-123 (ET(A) receptor antagonist) or BQ-788 (ET(B) receptor antagonist) was continuously infused into normal rats at the rate of 10 nmol/min for 10 min. The sinusoids were observed at 60 min after the infusion by scanning electron microscopy. The localization of ET-1 and ET(A) and ET(B) receptors was examined by the indirect immunoperoxidase method.
When BQ-123 was infused, the portal pressure gradually decreased with time, and it showed a significant reduction compared with the control groups. On the other hand, a decrease in portal pressure was not evident in the BQ-788-infused groups. Hepatic tissue blood flow was maintained at the value prior to the infusion in both groups. BQ-123 also caused a marked dilatation of the SEF. The diameters of the SEF after BQ-123 infusion were almost three times those of normal SEF. ET-1 was evenly present along the sinusoidal walls, and the reaction products of the ET(A) receptors were recognized along the portal vein and in the sinusoidal cells, that is, the hepatic stellate cells and endothelial cells.
Action of ET-1 via the ET(A) receptors may regulate the size of SEF in addition to hepatic microcirculation.
肝血窦内皮窗孔（SEF）通过改变其直径和数量来调节肝血窦循环。本研究记录了内皮素（ET）受体拮抗剂对SEF和肝微循环的影响。
分别用液压计和激光多普勒血流仪测量门静脉压力和肝组织血流量。将BQ-123（ET(A)受体拮抗剂）或BQ-788（ET(B)受体拮抗剂）以10 nmol/min的速率持续输注到正常大鼠体内10分钟。输注后60分钟通过扫描电子显微镜观察肝血窦。采用间接免疫过氧化物酶法检测ET-1及ET(A)和ET(B)受体的定位。
输注BQ-123时，门静脉压力随时间逐渐降低，与对照组相比有显著下降。另一方面，输注BQ-788的组门静脉压力下降不明显。两组肝组织血流量均维持在输注前的水平。BQ-123还导致SEF明显扩张。输注BQ-123后SEF的直径几乎是正常SEF的三倍。ET-1沿肝血窦壁均匀分布，ET(A)受体的反应产物在门静脉及肝血窦细胞即肝星状细胞和内皮细胞中被识别。
ET-1通过ET(A)受体的作用除了调节肝微循环外，还可能调节SEF的大小。
