Oshita M, Takei Y, Kawano S, Yoshihara H, Hijioka T, Fukui H, Goto M, Masuda E, Nishimura Y, Fusamoto H
First Department of Medicine, Osaka University Medical School, Japan.
J Clin Invest. 1993 Apr;91(4):1337-42. doi: 10.1172/JCI116334.
This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol.
本研究旨在探讨乙醇诱导离体灌注大鼠肝脏血管收缩的机制。当以25至100 mM的浓度开始向门静脉输注乙醇时，门静脉压力开始以浓度依赖性方式升高，并在2 - 5分钟内达到最高水平（初始阶段），随后在乙醇输注期间逐渐下降（逃逸现象）。内皮素-1抗血清显著抑制这种乙醇诱导的肝脏血管收缩达45 - 80%。停止输注内皮素-1抗血清后，门静脉压力随后升高。另一方面，当一氧化氮合成抑制剂N-甲基-L-精氨酸（L-NMMA）与乙醇同时注入门静脉时，门静脉压力对乙醇反应的初始阶段未改变，门静脉压力峰值保持不变。然而，在门静脉压力达到峰值升高后，下降速率低于未使用L-NMMA时。因此，L-NMMA减弱了逃逸现象并维持了血管收缩。本研究支持以下假说：两种内皮源性血管活性因子，即内皮素-1和一氧化氮，在乙醇存在的情况下调节肝脏血管张力。
