Department of Internal Medicine II, School of Medicine, University Hospital, Regensburg, Germany.
Am J Physiol Gastrointest Liver Physiol. 2009 Oct;297(4):G849-57. doi: 10.1152/ajpgi.00084.2009. Epub 2009 Aug 20.
Splanchnic vasodilation is the pathophysiological hallmark in the development of the hyperdynamic circulatory syndrome in liver cirrhosis and portal hypertension. This has been attributed so far mainly to a marked vascular hyporeactivity to endogenous vasoconstrictors. However, myogenic tone and vessel stiffness have not been addressed in mesenteric arteries in liver cirrhosis. CCl(4)(-)-induced ascitic cirrhotic (LC) and age-matched control rats, portal vein-ligated (PVL) rats, and sham-operated rats were investigated. Third-order mesenteric resistance arteries were studied under no-flow conditions using a pressure myograph measuring media thickness and lumen diameter in response to incremental increases in intramural pressure, from which wall mechanics were calculated. Electron microscopy was used for investigation of wall ultrastructure, especially the fenestrae in internal elastic lamina (IEL). In PVL animals, no significant change in passive vessel strain, stress, media-to-lumen ratio, or cross-sectional area was noted. In contrast, in LC rats, vessel strain was markedly elevated compared with healthy control rats, indicating a marked reduction in vessel stiffness. In addition, the strain-stress curve was shifted to the right, and the elastic modulus in dependency on vessel stress decreased, demonstrating predominantly structure-dependent factors to be involved. The media-to-lumen quotient was not significantly altered, but cross-sectional area was highly increased in LC rats, indicating hypertrophic outward remodeling. These findings were paralleled by enlarged fenestrae in the IEL but no change in thickness of IEL or proportion of extracellular matrix or vascular smooth muscle in LC rats. We concluded that, in long-standing severe portal hypertension such as ascitic LC but not in short-term conditions such as PVL, mesenteric resistance arteries exhibit vascular remodeling and markedly less resistant mechanical properties, leading to decreased vessel stiffness accompanied by structural changes in the IEL. This may well contribute to the maintenance and severity of splanchnic arterial vasodilation in LC.
内脏血管舒张是肝硬化和门静脉高压症高动力循环综合征发展的病理生理标志。到目前为止，这主要归因于内源性血管收缩剂对血管的反应性显著降低。然而，在肝硬化的肠系膜动脉中，肌源性张力和血管僵硬尚未得到解决。用压力肌动描记术测量对腔内压力递增反应的中膜厚度和管腔直径，在无血流条件下研究了第 3 级肠系膜阻力动脉，从中计算出壁力学。电子显微镜用于研究壁超微结构，特别是内部弹性膜（IEL）中的窗孔。在门静脉结扎（PVL）动物中，被动血管应变、应力、中膜与管腔比或横截面积没有明显变化。相比之下，在 LC 大鼠中，血管应变明显高于健康对照组大鼠，表明血管僵硬显著降低。此外，应变-应力曲线向右移位，依赖于血管应力的弹性模量降低，表明主要涉及结构依赖性因素。中膜与管腔比值没有明显改变，但 LC 大鼠的横截面积显著增加，表明呈向外的肥大性重塑。这些发现与 IEL 中窗孔增大以及 LC 大鼠中 IEL 厚度、细胞外基质或血管平滑肌比例没有变化平行。我们得出结论，在长期严重的门静脉高压（如腹水性 LC）中，但不在短期条件（如 PVL）中，肠系膜阻力动脉表现出血管重塑和显著降低的机械阻力特性，导致血管僵硬降低，同时 IEL 发生结构变化。这很可能有助于维持和加重 LC 内脏动脉舒张。
