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Effect of adrenomedullin on the activity of barosensitive neurons in the rostral ventrolateral medulla of rats
Pages: 193-200
Year: Issue:  3

Keyword:  adrenomedullinreceptornitric oxiderostral ventrolateral medullaiontophoresisextracellular recording;
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 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.
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