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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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Citing This Article：

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).