Effect of adrenomedullin on the activity of barosensitive neurons in the rostral ventrolateral medulla of rats
- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 3
- DOI:
- 10.3321/j.issn:0371-0874.2006.03.001
- Key Word:
- 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;adrenomedullin;receptor;nitric oxide;rostral ventrolateral medulla;iontophoresis;extracellular 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.
- [1]季淑梅,何瑞荣.延髓腹外侧头端区注射肾上腺髓质素对大鼠血压、心率和肾交感神经活动的影响[J].2002,(6).
- [2]Dampney RA,Tagawa T,Fontes MA,etc.Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone.[J].2003,177(3).
- [3]K R, Oliver,A, Wainwright,R P, Heavens,etc.Distribution of novel CGRP1 receptor and adrenomedullin receptor mRNAs in the rat central nervous system.[J].1998,57.
- [4]Smith PM,Ferguson AV.Adrenomedullin acts in the rat paraventricular nucleus to decrease blood pressure.[J].2001,13(5).
- [5]A A, Owji,D M, Smith,H A, Coppock,etc.An abundant and specific binding site for the novel vasodilator adrenomedullin in the rat.[J].1995,136.
- [6]Hinson JP,Kapas S,Smith DM.Adrenomedullin, a multifunctional regulatory peptide.[J].2000,21(2).
- [7]Yong, Xu,Teresa L, Krukoff.Adrenomedullin in the rostral ventrolateral medulla increases arterial pressure and heart rate: roles of glutamate and nitric oxide.[J].2004,287.
- [8]Ally A,Ishide T,Maher TJ.Role of nitric oxide in the ventrolateral medulla on cardiovascular responses and glutamate neurotransmission during mechanical and thermal stimuli.[J].2003,47(1).
- [9]Satoh F,Takahashi K,Murakami O,etc.Adrenomedullin in human brain, adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma.[J].1995.
- [10]Gallardo JR,Martinez-Murillo R,Fernandez AP,etc.Distribution of adrenomedullin-like immunoreactivity in the rat central nervous system by light and electron microscopy.[J].2000,853(2).
- [11]Xu Y,Krukoff TL.Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by nitric oxide and GABA.[J].2004,119(1).
- [12]Rossier BC,Firsov D,Flahaut M,etc.N-Glycosylation and Conserved Cysteine Residues in RAMP3 Play a Critical Role for the Functional Expression of CRLR/RAMP3 Adrenomedullin Receptor.[J].2003,42(34).
- [13]Koblan KS,Wainwright A,Hill RG,etc.Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat.[J].2001,14(4).
- [14]John Chalmers,Paul Pilowsky.Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure[J].1991,9(8).
- [15]Martins-Pinge M. C.,Baraldi-Passy I.,Lopes O. U..Excitatory Effects of Nitric Oxide Within the Rostral Ventrolateral Medulla of Freely Moving Rats[J].1997.
- [16]R A, Dampney.The subretrofacial vasomotor nucleus: anatomical, chemical and pharmacological properties and role in cardiovascular regulation.[J].1994,42(2).