Takashimizu Shinji, Kojima Seiichiro, Nishizaki Yasuhiro, Kagawa Tatehiro, Shiraishi Koichi, Mine Tetsuya, Watanabe Norihito
Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Japan.
Tokai J Exp Clin Med. 2011 Jul 20;36(2):37-43.
The effect of an endothelin (ET) A receptor antagonist on hepatic hemodynamics in cirrhotic rats was examined.
Portal pressure and hepatic tissue blood flow in cirrhotic rats were measured. Plasma ET-1 levels were determined by radioimmunoassay. BQ-123 was infused to these rats at a rate of 10 nmol/min. The sinusoids were observed by scanning electron microscopy. The localization of ET-1 and ETA receptors was examined using the indirect immunoperoxidase method.
In cirrhotic rats, the portal pressure significantly increased to 16.6 ± 1.5 cm H2O, and the hepatic tissue blood flow markedly decreased. Plasma ET-1 levels in cirrhotic rats were higher than those in normal rats. When BQ-123 was infused, the portal pressure was significantly reduced by more than 2 cm H2O, compared with the control group (p < 0.05). Hepatic tissue blood flow was maintained at the level before infusion. In liver cirrhosis, the sinusoids were covered with continuous endothelial cells, and the number of sinusoidal endothelial fenestrae extremely decreased. ET-1 was remarkably enhanced in sinusoidal endothelial cells within the regenerating nodules, and the reaction products of ETA receptors were mainly recognized in hepatic stellate cells.
The augmented action of ET-1 via the ETA receptor may be involved in the mechanism of portal hypertension in liver cirrhosis.
研究内皮素（ET）A受体拮抗剂对肝硬化大鼠肝脏血流动力学的影响。
测量肝硬化大鼠的门静脉压力和肝组织血流量。采用放射免疫分析法测定血浆ET-1水平。以10 nmol/min的速率向这些大鼠输注BQ-123。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和ETA受体的定位。
肝硬化大鼠门静脉压力显著升高至16.6±1.5 cm H₂O，肝组织血流量明显减少。肝硬化大鼠血浆ET-1水平高于正常大鼠。输注BQ-123时，与对照组相比，门静脉压力显著降低超过2 cm H₂O（p<0.05）。肝组织血流量维持在输注前水平。在肝硬化中，肝血窦被连续的内皮细胞覆盖，肝血窦内皮窗孔数量极度减少。再生结节内的肝血窦内皮细胞中ET-1显著增强，ETA受体的反应产物主要在肝星状细胞中被识别。
ET-1通过ETA受体的增强作用可能参与了肝硬化门静脉高压的机制。
