Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation
Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation
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DOI：
10.1113/jphysiol.2007.129031
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发表时间：
2007-06-15
影响因子：
5.5
通讯作者：
Machado, Benedito H.
中科院分区：
文献类型：
--
作者：
Braga, Valdir A.;Soriano, Renato N.;Machado, Benedito H.
用氰化钾（KCN）激活清醒大鼠或工作中的心-脑干准备（WHBP）的外周化学反射，产生：（a）交感神经兴奋/升压反应;（B）心动过缓;（c）呼吸频率增加。我们的主要目的是评估神经递质参与介导的交感神经兴奋成分的化学反射内孤束核（NTS）。在以往的研究中，在清醒的大鼠，反射性心动过缓，但不是升压反应，减少了拮抗离子型谷氨酸或嘌呤能P2受体的NTS内。在本研究中，我们评估了可能的双重作用的P2和NMDA受体在NTS处理交感神经兴奋成分（升压反应）的化学反射清醒大鼠以及在WHBP。连续微量注射犬尿烯酸同时阻断离子型谷氨酸受体和P2受体（KYN，2 nmol（50 nl）（-1））和磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸盐（泛非发展战略，0.25 nmol（50 nl）（-1））注入清醒大鼠的连合孤束核（NTS），引起升压和舒张功能的显著降低。（+38 +/- 3 vs +8 +/- 3 mmHg）和心动过缓反应（-172 +/- 18对比-16 +/- 13次/分（-1）; n = 13），但使用体积描记法测量的呼吸急促无显著变化（270 +/- 30 vs 240 +/- 21个循环min（-1），n = 7）。控制微量注射生理盐水产生这些反射反应没有显着变化。在WHBP中，KYN显微注射（2 nmol（20 nl）（-1））和PPADS（1.6 nmol（20 nl）（-1））注入连合NTS显著减弱胸交感神经活动的增加，（+52 +/- 2% vs +17 +/- 1%）和心动过缓反应（-151 +/-17对-21 +/-3次/分（-1）），但对膈神经放电频率的增加无显著变化（+0.24 +/- 0.02+0.20 +/- 0.02 Hz）。这些数据表明，PPADS和KYN的联合微量注射到连合NTS在清醒的大鼠和WHBP需要产生显着减少的交感神经兴奋性反应（升压反应）外周化学反射激活。我们的结论是，多巴胺能和嘌呤能机制的化学反射的交感神经兴奋成分在连合NTS的水平的复杂的神经传递系统的一部分。
Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats or in the working heart-brainstem preparation (WHBP) produces: (a) a sympathoexcitatory/pressor response; (b) bradycardia; and (c) an increase in the frequency of breathing. Our main aim was to evaluate neurotransmitters involved in mediating the sympathoexcitatory component of the chemoreflex within the nucleus tractus solitarii (NTS). In previous studies in conscious rats, the reflex bradycardia, but not the pressor response, was reduced by antagonism of either ionotropic glutamate or purinergic P2 receptors within the NTS. In the present study we evaluated a possible dual role of both P2 and NMDA receptors in the NTS for processing the sympathoexcitatory component (pressor response) of the chemoreflex in awake rats as well as in the WHBP. Simultaneous blockade of ionotropic glutamate receptors and P2 receptors by sequential microinjections of kynurenic acid (KYN, 2 nmol (50 nl)(-1)) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS, 0.25 nmol (50 nl)(-1)) into the commissural NTS in awake rats produced a significant reduction in both the pressor (+38 +/- 3 versus +8 +/- 3 mmHg) and bradycardic responses (-172 +/- 18 versus -16 +/- 13 beats min(-1); n = 13), but no significant changes in the tachypnoea measured using plethysmography (270 +/- 30 versus 240 +/- 21 cycles min(-1), n = 7) following chemoreflex activation in awake rats. Control microinjections of saline produced no significant changes in these reflex responses. In WHBP, microinjection of KYN (2 nmol (20 nl)(-1)) and PPADS (1.6 nmol (20 nl)(-1)) into the commissural NTS attenuated significantly both the increase in thoracic sympathetic activity (+52 +/- 2% versus +17 +/- 1%) and the bradycardic response (-151 +/- 17 versus -21 +/- 3 beats min(-1)) but produced no significant changes in the increase of the frequency of phrenic nerve discharge (+0.24 +/- 0.02+0.20 +/- 0.02 Hz). The data indicate that combined microinjections of PPADS and KYN into the commissural NTS in both awake rats and the WHBP are required to produce a significant reduction in the sympathoexcitatory response (pressor response) to peripheral chemoreflex activation. We conclude that glutamatergic and purinergic mechanisms are part of the complex neurotransmission system of the sympathoexcitatory component of the chemoreflex at the level of the commissural NTS.