【摘要】 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。更多还原

【Abstract】 To investigate the eletrophysiological effect of rat adrenomedullin (rADM) on barosensitive neurons in the rostral ventrolat- eral 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 30,60 and 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.更多还原