Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
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DOI：
10.1152/ajpgi.00336.2005
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发表时间：
2006-05-01
影响因子：
4.5
通讯作者：
Groszmann, RJ
中科院分区：
文献类型：
--
作者：
Abraldes, JG;Iwakiri, Y;Groszmann, RJ
一氧化氮（NO）的增加是导致与晚期门静脉高压症（PHT）相关的高动力循环的主要因素，但触发NO产生所需的门静脉压力增加的初始机制和幅度尚不清楚。我们通过研究不同程度门脉高压大鼠的全身和内脏血流动力学以及内皮型一氧化氮合酶（eNOS）和VEGF的表达来解决这些问题。用三种不同口径（16、18和20号）的针头进行门静脉结扎（PVL），产生了不同程度的PHT和门体分流。与假手术组相比，PVL组大鼠均表现出高动力循环特征。最小门静脉高压症大鼠（PVL与16号针）显示了早期增加VEGF和eNOS表达选择性在空肠。免疫荧光显示VEGF表达位于粘膜的高度血管化区域。VEGF信号的抑制显著减弱eNOS表达的增加。总之，门静脉压力的轻度增加足以上调肠微循环中的eNOS，并且这至少部分地通过VEGF上调而发生。
Increased nitric oxide (NO) is the main factor leading to the hyperdynamic circulation associated with advanced portal hypertension (PHT), but the initial mechanisms and the magnitude of increase in portal pressure required to trigger NO production are not known. We addressed these issues by studying systemic and splanchnic hemodynamics and endothelial NO synthase (eNOS) and VEGF expression in rats with different degrees of portal hypertension. Portal vein ligation (PVL) performed over needles of three different calibers (16-, 18-, and 20-gauge) yielded different degrees of PHT and portosystemic shunting. Compared with sham rats, all three groups of PVL rats exhibited features of hyperdynamic circulation. Rats with minimal portal hypertension (PVL with a 16- gauge needle) showed an early increase in VEGF and eNOS expression selectively at the jejunum. Immunofluorescence showed that VEGF expression was located in highly vascularized areas of the mucosa. Inhibition of VEGF signaling markedly attenuated the increase in eNOS expression. In conclusion, mild increases in portal pressure are enough to upregulate eNOS at the intestinal microcirculation, and this occurs, at least in part, through VEGF upregulation.