Fan Ming-Xin, Li Xia, Wang Jin, Cao Yin-Xiang, Shen Lin-Lin, Zhu Da-Nian
Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Sheng Li Xue Bao. 2006 Jun 25;58(3):193-200.
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, 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 rADMjthe 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.
为研究大鼠肾上腺髓质素（rADM）对延髓头端腹外侧区（rVLM）压力感受性神经元的电生理效应及其潜在机制，采用细胞外记录和多管离子电泳方法。在rVLM的29个压力感受性神经元中，20个神经元对离子电泳施加的rADM表现出兴奋反应，在30、60和90 nA电流下，放电频率分别从（10.8±2.7）次/秒增加到（14.6±3.6）、（19.8±4.7）和（31.9±6.4）次/秒（P<0.05，n = 20）。应用人肾上腺髓质素（22 - 52）[hADM（22 - 52）]，一种rADM受体的特异性拮抗剂，明显减弱了rADM诱导的放电频率增加；放电频率增加了15.4%[（11.4±2.5）次/秒，P<0.05，n = 10]。另一种拮抗剂，人降钙素基因相关肽（8 - 37）[hCGRP（8 - 37）]对rADM诱导的兴奋无显著影响。记录另外23个压力感受性神经元以测试一氧化氮合酶（NOS）抑制剂对rADM兴奋效应的影响。在10个神经元中，7 - NiNa（神经元型NOS抑制剂）在10、20和40 nA电流下，分别将放电频率从（10.1±3.5）次/秒降低到（7.5±2.5）、（5.3±2.1）和（3.1±1.4）次/秒（P<0.05，n = 10）。在应用7 - NiNa期间，rADM（60 nA，30秒）的兴奋效应几乎被消除，放电频率仅比基础水平（6.2±1.9）次/秒增加了17%（P<0.05，n = 7）。而在8个压力感受性神经元中，氨基胍（AG，诱导型NOS抑制剂）在10、20和40 nA电流下，分别将静息水平的放电频率从（11.5±5.1）次/秒增加到（17.8±5.6）、（22.5±6.3）和（29.1±6.4）次/秒（P<0.05，n = 8）。当在AG离子电泳期间给予rADM（60 nA，30秒）时，放电频率比基础水平显著增加了60%[（22.5±6.3）次/秒，n = 5]。这些结果表明，rADM直接激活rVLM中的压力感受性神经元并作为心血管调节因子发挥作用，并且该功能可能由其特异性受体介导。NO，主要源自神经元型NOS，可能参与rADM在rVLM中的兴奋效应。
