Hartleb M, Michielsen P P, Dziurkowska-Marek A
Clinical Department of Gastroenterology, Silesian Medical School, Katowice, Poland.
Acta Gastroenterol Belg. 1997 Jul-Sep;60(3):222-32.
Hypotension, low systemic vascular resistance and reduced sensitivity to vasoconstrictor are features of hyperdynamic syndrome in portal hypertension (PH) and are pathogenetic factors triggering most serious clinical complications of liver cirrhosis. Nitric oxide (NO) is a powerful vasodilating agent, released from vascular endothelium cell and effecting relaxation of vascular smooth muscle. An increased release of NO has been proposed to play a role in the pathogenesis of vasodilation and vascular hypocontractility associated with PH. In agreement with this hypothesis, the whole-body production of NO has been found to be increased in PH, and the measurement of NOS mRNA expression in different organs suggest that the splanchnic vascular system is a major source of NO release. Consequently, NO could play a role in the development of the splanchnic hyperaemia, collateral circulation and portal hypertensive gastropathy. Furthermore, increased generation of NO in central circulation likely accounts for pulmonary vasorelaxation and cardiac dysfunction found in cirrhosis. By contrast, PH-associated endothelial dysfunction seems to invalidate the capability of intrahepatic and intrarenal vasculature to produce NO. A deficient NO release in these vascular territories might contribute to enhancement of PH and development of the hepatorenal syndrome. Overall NO hyperproduction is either the cause (induction of iNOS) or the consequence (stimulation of ecNOS) of the hyperdynamic syndrome. This incertitude results from the yet undefined significance of mild and transitory activation of the endotoxin-cytokines axis for iNOS induction and contradictory data on specific iNOS and ecNOS activities. A contribution of each isoform of NOS to pathogenesis of the hyperdynamic syndrome probably depends on the model of PH in animal studies and the aetiology or severity of cirrhosis in human studies.
低血压、低全身血管阻力以及对血管收缩剂的敏感性降低是门静脉高压（PH）高动力综合征的特征，也是引发肝硬化最严重临床并发症的致病因素。一氧化氮（NO）是一种强大的血管舒张剂，由血管内皮细胞释放，可使血管平滑肌松弛。有人提出，NO释放增加在与PH相关的血管舒张和血管收缩功能减退的发病机制中起作用。与这一假设一致，已发现PH患者全身NO生成增加，对不同器官中NOS mRNA表达的测量表明，内脏血管系统是NO释放的主要来源。因此，NO可能在内脏充血、侧支循环和门静脉高压性胃病的发展中起作用。此外，中央循环中NO生成增加可能是肝硬化患者出现肺血管舒张和心脏功能障碍的原因。相比之下，与PH相关的内皮功能障碍似乎使肝内和肾内血管系统产生NO的能力失效。这些血管区域中NO释放不足可能会导致PH加重和肝肾综合征的发展。总体而言，NO过度生成要么是高动力综合征的原因（诱导诱导型一氧化氮合酶），要么是其结果（刺激内皮型一氧化氮合酶）。这种不确定性源于内毒素-细胞因子轴轻度和短暂激活对诱导型一氧化氮合酶诱导的意义尚未明确，以及关于特定诱导型一氧化氮合酶和内皮型一氧化氮合酶活性的矛盾数据。在动物研究中，一氧化氮合酶的每种同工型对高动力综合征发病机制的贡献可能取决于PH模型，而在人体研究中则取决于肝硬化的病因或严重程度。
