The Study On The Regulatory Mechanism Of ET-1,NO,PGL₂ And C-Type Natriuretic Peptide On Hyperdynamic Circulation In Hepatic Cirrhosis And Portal Hypertension

Portal hypertension(PHT) is a circulatory consequence of increased portal blood flow and intrahepatic vascular resistance. The majority of the increased intrahepatic resistance observed in cirrhosis and PHT is caused by structural changes such as the fibrosis and regenerative nodules, meanwhile, there exists disorders of multiple vasoactive substances(VAS) which lead to the changes of vascular tone. VAS can not only constrict hepatic vessel to increase intrahepatic resistance but also relax splanchnic vessel to increase splanchnic and portal blood flow. ET-1,NO,PGI2 are three of the major VAS. Recent studies has shown that they play a major role in the disturbance of hemodynamics in PHT. During the development of PHT, the effects of ET-1,NO and PGI2 as well as the interaction of them on hepatic and splanchnic circulation do not constantly unchange, although it has not been clearly defined how they changed. In different stages of hepatic cirrhosis, ET-l,NO,PGl2 may play different role and the same VAS may posess different functions and activities in different vascular beds. Up to now there are few reports of the modified regularity of the action and interaction of NO, ET-1 and PGI2 on the hepatic and splanchnic vascular beds with the development of hepatic cirrhosis. This study investigated the effects of ET-1, NO, PGI2 and their interactions on the hepatic hemodynamics with technique of isolated perfused liver to exclude the interferences of other VAS in different cirrhotic stages.CNP is one of the endothelial vasodilators. Recently it has been shown that CNP could reduce the portal pressure of hepatic cirrhotic rats. Up todate, the machanism of CNP in the pathogenisis of PHT is not elucidated. There are few reports of the effect of CNP, and its interactions with NO,ET-1 and PGIi on the hemodynamic disorders in cirrhosis. This study evaluated the effects of CNP on hepatic and mesenteric circulations and its interaction with NO,ET-1 and PGI2 with technique of isolated liver perfusion and in situ mesenteric perfusion.This study may provide the theory basis to elucidate the pathogenisis of PHT and direct clinical treatments.1 The Effects of ET-1 on hepatic hemodynamics in isolated perfused rat liver of cirrhosis1.1 Objective: To evaluate the effects of ET-1 on the hepatic hemodynamics and the type of mediated receptors in isolated perfused rat liver of early and late cirrhotic stages.1.2 Methods: Hepatic cirrhosis was induced by an intraperitoneal injection of CCL4(50%,0.3ml/100g,twice a week).In the 9th(E-HC) and H^L-HC) weekend after injected CCL4, the isolated perfusion of liver was performed at a constant flow rate to determine the effects of ET-1 (concentration ranging from 0.1 to l0nM) and the type of mediated receptor on the hepatic resistance. The hepatic resistance was estimated using the inflow pressure-PP and the outflow pressure-Phv.1.3 Results1.3.1 The portal pressure(Ppv) of the L-HC (2.364+0.29) was higher than that of the E-HC group (1.542+0.21,P<0.01),both of them were higher than that of the controls(1.183+0.13,P<0.01).The mean arterial pressure (MAP) of the L-HC(12.363+1.34) was significant lower than that of the E-HC(14.586+1.31,P<0.01)and control group(14.444+1.29, PO.01), the MAP of the E-HC and control group were not significant difference (P>0.05). The heart rates of the L-HC rats(335.500+17.43) increased significantly than the E-HC(310.130+21.08) and control group (305.500+16.06) (P<0.01).There were no differences between the heart rates of the E-HCand control group(P>0.05).1.3.2 The portal perfused pressure(PP) of the L-HC (1.464+0.17) in baseline state was higher than that of the E-HC(1.163+0.13, P0.01), both of them were higher than that of the controls (0.845+0.10, P0.01). There were no differences among these three groups in hepatic vein pressure (Phv) (P>0.05).1.3.3 The PP increased significantly at concentrations higher than 0.1 nM in a dose-dependent manner. On the contrary, there showed no changes of Phv even a...