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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

樊明欣, 李霞, 王锦, 曹银祥, 沈霖霖, 朱大年

复旦大学上海医学院生理学与病理生理学系.上海 200032

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 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({sl P}<0.05,{sl 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,{sl P}<0.05,{sl 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 ({sl P}<0.05, {sl n}=10)。在微电泳7--NiNa过程中同时微电泳ADM，则ADM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个神经元以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 ({sl P}<0.05, {sl n}=8)，ADM与AG同时微电泳时，AG对ADM本身增加神经元放电的效应无明显影响。上述结果提示，ADM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。

关键词： 肾上腺髓质素; 受体; 一氧化氮; 延髓头端腹外侧区; 微电泳; 细胞外记录

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

Fan Mingxin, Li Xia, Wang Jin, Cao Yinxiang, Shen Linlin, Zhu Danian

Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University.Shanghai 200032

Abstract

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 rat ADM (rADM) and increased their 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 increase of firing rate was about 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 nearly eliminated and the magnitude of firing rate decreased to about 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 from (11.5±5.1) spikes/s of the resting level 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 aminoguanidine 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 nNOS originated might be involved in the excitatory effect of ADM in the rVLM.

Key words: Adrenomedullin;Receptor;Nitric oxide;Rostral ventrolateral medulla;iontophoresis;Extracellular recording

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引用本文：

樊明欣, 李霞, 王锦, 曹银祥, 沈霖霖, 朱大年. 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[J]. 生理学报 2006; 58 (3): .

Fan Mingxin, Li Xia, Wang Jin, Cao Yinxiang, Shen Linlin, Zhu Danian. Effect of adrenomedullin on the activity of barosensitive neurons in the rostral ventrolaterai medulla of rats. Acta Physiol Sin 2006; 58 (3): (in Chinese with English abstract).