CAJ | 학술논문

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 ventrolateral 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90 nA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40 nA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40 nA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对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.
채용다관미전영결합세포외기록적방법연구료신상선수질소(adrenomedullin,ADM)대대서연수두단복외측구(rostral ventrolateral medulla,rVLM)압력반사민감성신경원전활동적작용급기가능궤제.결과현시:재29개rVLM압력반사민감신경원중,20개신경원재30、60화90 nA적전류미전영대서ADM(rADM)과정중,방전빈솔유(10.8±2.7)spikes/s분별증가도(14.6±3.6)、(19.8±4.7)화(31.9±6.4)spikes/s(P＜0.05,n=20).미전영rADM특이성수체조단제인ADM(human ADM,hADM)(22-52)가명현감소신경원방전빈솔적증가폭도,비정상방전빈솔부증가15.4%[(11.4±2.5)sipkes/s,P＜0.05,n=10],이강개소기인상관태1(CGRP1)수체조단제hCGRP(8-37)대rADM흥강성신경원전활동영향교소.재령외23개신경원중,10개신경원적방전빈솔재10、20화40 nA전류미전영신경형NOS(nNOS)억제제7-NiNa과정중방전감소,유정상적(10.1±3.5)spikes/s분별감소위(7.5±2.5)、(5.3±2.1)화(3.1±1.4)spikes/s(P＜0.05,n=10).재미전영7-NiNa과정중동시미전영rADM,칙rADM증가신경원방전빈솔적효응감약,증가폭도위기출수평적17%[(6.2±1.9)spikes/s].8개신경원재10、20화40 nA전류미전영유도형NOS억제제(iNOS)aminoguanidine(AG)과정중방전빈솔유(11.5±5.1)spikes/s증가도(17.8±5.6)、(22.5±6.3)화(29.1±6.4)spikes/s(P＜0.05,n=8),rADM여AG동시미전영시,AG대rADM본신증가신경원방전적효응무명현영향.상술결과제시,rADM재rVLM가통과기특이성수체혹래원우nNOS적NO작용우압력반사민감신경원,사기활동증강이발휘조절심혈관활동적작용.
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.