Bátkai S, Járai Z, Wagner J A, Goparaju S K, Varga K, Liu J, Wang L, Mirshahi F, Khanolkar A D, Makriyannis A, Urbaschek R, Garcia N, Sanyal A J, Kunos G
National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Nat Med. 2001 Jul;7(7):827-32. doi: 10.1038/89953.
Advanced cirrhosis is associated with generalized vasodilation of unknown origin, which contributes to mortality. Cirrhotic patients are endotoxemic, and activation of vascular cannabinoid CB1 receptors has been implicated in endotoxin-induced hypotension. Here we show that rats with biliary cirrhosis have low blood pressure, which is elevated by the CB1 receptor antagonist SR141716A. The low blood pressure of rats with CCl4-induced cirrhosis was similarly reversed by SR141716A, which also reduced the elevated mesenteric blood flow and portal pressure. Monocytes from cirrhotic but not control patients or rats elicited SR141716A-sensitive hypotension in normal recipient rats and showed significantly elevated levels of anandamide. Compared with non-cirrhotic controls, in cirrhotic human livers there was a three-fold increase in CB1 receptors on isolated vascular endothelial cells. These results implicate anandamide and vascular CB1 receptors in the vasodilated state in advanced cirrhosis and indicate a novel approach for its management.
晚期肝硬化与不明原因的全身血管舒张有关，这会导致死亡率上升。肝硬化患者存在内毒素血症，血管大麻素CB1受体的激活与内毒素诱导的低血压有关。在此我们表明，胆汁性肝硬化大鼠血压较低，而CB1受体拮抗剂SR141716A可使其血压升高。SR141716A同样能逆转四氯化碳诱导的肝硬化大鼠的低血压，还能降低升高的肠系膜血流量和门静脉压力。肝硬化患者而非对照患者或大鼠的单核细胞，在正常受体大鼠中引发了SR141716A敏感的低血压，并显示出明显升高的花生四烯乙醇胺水平。与非肝硬化对照组相比，在肝硬化患者肝脏中，分离的血管内皮细胞上的CB1受体增加了两倍。这些结果表明花生四烯乙醇胺和血管CB1受体与晚期肝硬化的血管舒张状态有关，并指出了一种新的治疗方法。
