Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium.
Gut. 2012 Apr;61(4):604-12. doi: 10.1136/gutjnl-2011-301396. Epub 2011 Dec 20.
The liver is innervated by the vagus nerve. Its efferent neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) are both well-known vasodilators. A study was undertaken to determine whether electrical vagus nerve stimulation (STIM) influences portal vein pressure.
The left vagus nerve upstream of the hepatic branch was stimulated at 5 Hz (ACh release) and 10 Hz (VIP release) in normal and cirrhotic rats.
STIM at both frequencies decreased portal pressure in normal rats while, in cirrhotic rats, only 10 Hz STIM resulted in long-lasting reduction of portal pressure. Hepatic branch vagotomy prevented the STIM-induced decrease in pressure, proving that the effect is a direct hepatic effect. Deafferentation of the left vagus nerve by pretreatment with capsaicin did not change the effect of STIM, showing that the vagus efferents and not the afferents are responsible for the decrease in portal pressure. Injecting microspheres before and after STIM showed that STIM did not lead to redistribution of systemic blood flow but decreased portal pressure by lowering intrahepatic resistance. Using in situ liver perfusion to evaluate the intrahepatic effect of ACh and VIP, both neurotransmitters significantly decreased the perfusion pressure in normal rats. VIP also decreased portal pressure in cirrhotic rats, confirming the results of STIM. This VIP-induced decrease in pressure could be prevented by a VIP receptor 2 antagonist. L-NAME did not inhibit the VIP effect in cirrhotic rats, indicating that VIP does not act via nitric oxide.
High-frequency electrical vagus stimulation improves portal hypertension in cirrhotic rats, most likely through release of VIP, binding to VIP receptor 2. As the technology is already in use for other applications, vagus nerve stimulation might be an important new strategy in the treatment of portal hypertension.
肝脏受迷走神经支配。其传出神经递质乙酰胆碱（ACh）和血管活性肠肽（VIP）都是众所周知的血管扩张剂。本研究旨在确定电刺激迷走神经（STIM）是否会影响门静脉压力。
在正常和肝硬化大鼠中，分别以 5 Hz（ACh 释放）和 10 Hz（VIP 释放）刺激肝支上游的左侧迷走神经。
两种频率的 STIM 均降低了正常大鼠的门静脉压力，而在肝硬化大鼠中，只有 10 Hz 的 STIM 导致门静脉压力持续降低。肝支迷走神经切断术阻止了 STIM 引起的压力下降，证明这种作用是直接的肝作用。预先用辣椒素来进行左侧迷走神经去传入神经处理不会改变 STIM 的作用，表明是迷走神经传出而不是传入纤维负责降低门静脉压力。在 STIM 前后注射微球显示 STIM 不会导致全身血流重新分布，而是通过降低肝内阻力来降低门静脉压力。使用原位肝灌注来评估 ACh 和 VIP 的肝内作用，这两种神经递质均显著降低了正常大鼠的灌注压。VIP 也降低了肝硬化大鼠的门静脉压力，证实了 STIM 的结果。这种 VIP 诱导的压力下降可以被 VIP 受体 2 拮抗剂所阻止。在肝硬化大鼠中，L-NAME 并未抑制 VIP 的作用，表明 VIP 不通过一氧化氮起作用。
高频电刺激迷走神经可改善肝硬化大鼠的门静脉高压，这很可能是通过释放 VIP，与 VIP 受体 2 结合来实现的。由于该技术已经用于其他应用，迷走神经刺激可能成为治疗门静脉高压的一种重要新策略。
