Objective: The effect of an endothelin (ET) A receptor antagonist on hepatic hemodynamics in cirrhotic rats was examined.
Methods: 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.
Results: 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.
Conclusions: The augmented action of ET-1 via the ETA receptor may be involved in the mechanism of portal hypertension in liver cirrhosis.