肾上腺髓质素对大鼠延髓头端腹外侧区压力反射敏感神经元的作用(英文)

Effect of adrenomedullin on the activity of barosensitive neurons in the rostral ventrolaterai medulla of rats

采用多管微电泳结合细胞外记录的方法研究了肾上腺髓质素(adrenomedullin,ADM)对大鼠延髓头端腹外侧区(rostral ven- trolateral medulla,rVLM)压力反射敏感性神经元电活动的作用及其可能机制。结果显示：在29个rVLM压力反射敏感神经元中,20个神经元在30、60和90nA的电流微电泳大鼠ADM(rADM)过程中,放电频率由(10．8±2．7)spikes/s分别增加到(14．6±3．6)、(19．8±4．7)和(31．9±6．4)spikes/s(P＜0．05,n=20)。微电泳rADM特异性受体阻断剂人ADM(human ADM,hADM) (22-52)可明显减小神经元放电频率的增加幅度,比正常放电频率仅增加15．4%[(11．4±2．5)sipkes/s,P＜0．05,n=10],而降钙素基因相关肽1(CGRP1)受体阻断剂hCGRP(8-37)对rADM兴奋性神经元电活动影响较小。在另外23个神经元中,10个神经元的放电频率在10、20和40nA电流微电泳神经型NOS(nNOS)抑制剂7-NiNa过程中放电减少,由正常的(10．1±3．5)spikes/s分别减少为(7．5±2．5)、(5．3±2．1)和(3．1±1．4)spikes/s(P＜0．05,n=10)。在微电泳7-NiNa过程中同时微电泳rADM,则rADM增加神经元放电频率的效应减弱,增加幅度为基础水平的17%[(6．2±1．9)spikes/s]。8个神经元在10、20和40nA电流微电泳诱导型NOS抑制剂(iNOS)aminoguanidine(AG)过程中放电频率由(11．5±5．1)spikes/s增加到(17．8±5．6)、(22．5±6．3)和(29．1±6．4) spikes/s(P＜0．05,n=8),rADM与AG同时微电泳时,AG埘rADM本身增加神经元放电的效应无明显影响。上述结果提示,rADM在rVLM可通过其特异性受体或来源于nNOS的NO作用于压力反射敏感神经元,使其活动增强而发挥调节心血管活动的作用。

To investigate the eletrophysiological effect of rat adrenomedullin （rADM） on barosensitive neurons in the rostral ventrolateral medulla （rVLM） and its potential mechanisms, the extracellular recording and multi-barrel iontophoresis methods were used. Of the 29 barosensitive neurons in the rVLM, 20 neurons demonstrated excitatory response to iontophoretically applied rADM and increased the firing rate from （10.8 ± 2.7） spikes/s to （14.6 ± 3.6）, （19.8 ± 4.7） and （31.9 ± 6.4） spikes/s （P＜0.05, n=20） at the current of 30, 60and 90 nA, respectively. Application of human adrenomedullin （22-52） [hADM （22-52）], a specific antagonist of rADM receptor,distinctly attenuated the augmentation of firing rate induced by rADM-the firing rate was increased by 15.4% [（11.4 ± 2.5） spikes/s, P＜0.05, n=10]. Another antagonist, human calcitonin gene-related peptide （8-37） [hCGRP （8-37）] had no significant effect on rADM-induced excitation. Other 23 barosensitive neurons were recorded to test the influence of nitric oxide synthase （NOS） inhibitors on the excitatory effect of rADM. In 10 neurons, 7-NiNa （neuronal NOS inhibitor） decreased the firing rate from （10.1 ± 3.5） spikes/s to （7.5 ± 2.5）, （5.3 ± 2.1） and （3.1 ± 1.4） spikes/s （P＜0.05, n=10） at the current of 10, 20 and 40 nA, respectively. The excitatory effect of rADM （60 nA, 30 s） during 7-NiNa application was nearly eliminated and the magnitude of firing rate was increased only by 17%of the basal level （6.2 ± 1.9） spikes/s （P＜0.05, n=7）. While aminoguanidine （AG, iNOS inhibitor） increased the firing rate at the resting level from （11.5 ± 5.1） spikes/s to （17.8 ± 5.6）, （22.5 ± 6.3） and （29.1 ± 6.4） spikes/s （P＜0.05, n=8） at the current of 10, 20 and 40 nA in 8 barosensitive neurons, respectively. When rADM （60 nA, 30 s） was delivered during AG iontophoresis period, the firing rate significantly increased by 60% of the basal level [（22.5 ± 6.3） spikes/s, n=5]. These results indicate that rADM activates the barosensitive neurons in the rVLM directly and acts as a cardiovascular regulator, and that this function might be mediated by its specific receptor. NO, mainly neuronal-NOS-originated might be involved in the excitatory effect of rADM in the rVLM.