ElectroCore LLC, Morris Plains, NJ, USA; and Department of Anesthesiology, Columbia University, New York, NY, USA.
Neuromodulation. 2012 Nov-Dec;15(6):527-36. doi: 10.1111/j.1525-1403.2012.00454.x. Epub 2012 May 2.
Electrical stimulation of the vagus nerve at relatively high voltages (e.g., >10 V) can induce bronchoconstriction. However, low voltage (≤2 V) vagus nerve stimulation (VNS) can attenuate histamine-invoked bronchoconstriction. Here, we identify the mechanism for this inhibition.
In urethanea-nesthetized guinea pigs, bipolar electrodes were attached to both vagus nerves and changes in pulmonary inflation pressure were recorded in response to i.v. histamine and during VNS. The attenuation of the histamine response by low-voltage VNS was then examined in the presence of pharmacologic inhibitors or nerve ligation.
Low-voltage VNS attenuated histamine-induced bronchoconstriction (4.4 ± 0.3 vs. 3.2 ± 0.2 cm H(2) O, p < 0.01) and remained effective following administration of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, and after sympathetic nerve depletion with guanethidine, but not after the β-adrenoceptor antagonist propranolol. Nerve ligation caudal to the electrodes did not block the inhibition but cephalic nerve ligation did. Low-voltage VNS increased circulating epinephrine and norepinephrine without but not with cephalic nerve ligation.
These results indicate that low-voltage VNS attenuates histamine-induced bronchoconstriction via activation of afferent nerves, resulting in a systemic increase in catecholamines likely arising from the adrenal medulla.
以相对较高的电压（例如，>10V）刺激迷走神经会引起支气管收缩。然而，低电压（≤2V）迷走神经刺激（VNS）可以减轻组胺引起的支气管收缩。在这里，我们确定了这种抑制的机制。
在乌拉坦麻醉的豚鼠中，将双极电极连接到两条迷走神经上，并记录静脉内给予组胺和 VNS 期间对肺充气压力的变化。然后，在存在药理抑制剂或神经结扎的情况下，检查低电压 VNS 对组胺反应的抑制作用。
低电压 VNS 减弱了组胺引起的支气管收缩（4.4±0.3 对 3.2±0.2cmH2O，p<0.01），并且在给予一氧化氮合酶抑制剂 NG-硝基-L-精氨酸甲酯和胍乙啶耗竭交感神经后仍然有效，但在β-肾上腺素能受体拮抗剂普萘洛尔后则不然。电极下游的神经结扎不能阻断抑制作用，但神经结扎在头部。低电压 VNS 增加了循环肾上腺素和去甲肾上腺素，但在头部神经结扎后则不然。
这些结果表明，低电压 VNS 通过激活传入神经减弱组胺引起的支气管收缩，导致儿茶酚胺的全身增加，可能来自肾上腺髓质。
