title: Effect of adrenomedullin on the activity of barosensitive neurons in the rostral ventrolateral medulla of rats.
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, 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.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Ming-Xin
authors.initials: MX
authors.lastname: Fan
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Yin-Xiang
authors.initials: YX
authors.lastname: Cao
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Shen
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Zhu
mesh_terms: D053607:Adrenomedullin / Q000502:physiology*; D000818:Animals; D055724:Electrophysiological Phenomena; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053607:Adrenomedullin; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat