Piva Anna, Zampieri Francesca, Di Pascoli Marco, Gatta Angelo, Sacerdoti David, Bolognesi Massimo
Clinica Medica 5, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.
Scand J Gastroenterol. 2012 Sep;47(8-9):1003-13. doi: 10.3109/00365521.2012.703231. Epub 2012 Jul 10.
In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis.
The effect of acute changes in intraluminal flow (0, 10, and 20 μl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 μm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration-response curves to phenylephrine were also obtained.
In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME.
Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.
在肝硬化中，内脏血管过度扩张是由于内源性血管舒张剂合成异常以及对血管收缩剂的敏感性降低。诸如壁面剪应力（WSS）等机械刺激在内脏循环中的作用仍不清楚。本研究的目的是在肝硬化实验模型中评估壁面剪应力（WSS）诱导的血管舒张以及肠系膜动脉血流的急性变化。
评估管腔内流量（0、10和20 μl/min）和WSS的急性变化对对照大鼠和肝硬化大鼠肠系膜动脉（直径<500 μm）直径的影响，分别在基线时以及抑制一氧化氮合酶、环氧化酶和血红素加氧酶后进行评估。还获得了对去氧肾上腺素的浓度 - 反应曲线。
在对照组中，管腔内流量增加导致动脉直径显著增加（p < 0.05），而WSS保持稳定；在用去氧肾上腺素预收缩的血管中该效应得以维持，吲哚美辛和L - 精氨酸甲酯可阻断该效应，随后添加中卟啉铬可恢复该效应（p < 0.05）。在肝硬化动脉中，无论是在基线时还是在暴露于吲哚美辛和L - 精氨酸甲酯后，动脉直径对流量的急性增加均无变化，但WSS增加（p < 0.01）。在动脉暴露于除吲哚美辛和L - 精氨酸甲酯之外的中卟啉铬后，对流量的反应性部分恢复（p < 0.05）。
肝硬化大鼠的动脉对流量的急性变化反应消失，这使肠系膜内皮暴露于WSS的突然变化中。
