Objective: To investigate the effects of ET-1 on isolated perfused rat liver and vascular rings at early and late stages of cirrhosis.
Methods: Liver cirrhosis was induced by an intraperitoneal injection of 50% CCl(4) (0.3 ml/100 g, twice a week). In the 9th and 14th weekend after injecting CCl(4), the isolated perfused liver and vascular rings were performed to evaluate effects of four concentrations of ET-1 on early and late stages of cirrhosis.
Results: The Ppv of L-HC group at baseline was higher than that of E-HC group, both were higher than that of the controls. However, there showed no differences on Phv in these groups. With the concentration of ET-1 increasing, PVP was elevated accordingly in E-HC and L-HC group. L-HC group showed higher PVP compared with E-HC group, both were higher than the controls. While in isolated vascular rings, with the deteriorating of cirrhosis, the cumulative response curves showed right-shift. 0.1 nmol/L ET-1 showed mild relaxation on vascular rings in L-HC group.
Conclusion: ET-1 can increase the PVP, especially with the deterioration of cirrhosis, there showed higher reaction compared with normal controls. The vascular rings showed low response on the contrary. So ET-1 plays an important role in the pathogenesis of portal hypertension. In view of its different roles on liver and vascular rings at early and late stages, administration of different selective antagonist of ET receptor at different stages of cirrhosis should be well considered.
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