Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats.
Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats.
复制标题
慢性间歇性缺氧会损害 F344 大鼠的心率对 AMPA 和 NMDA 的反应，并诱导模糊核中谷氨酸受体神经元的损失。
DOI：
10.1152/ajpregu.90412.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Cheng,ZixiJack
中科院分区：
文献类型：
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作者：
Yan,Binbin;Li,Lihua;Harden,ScottW;Gozal,David;Lin,Ying;Wead,WilliamB;Wurster,RobertD;Cheng,ZixiJack
Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) andN-methyl-d-aspartate (NMDA) receptors in the nucleus ambiguus (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3–4 mo) were exposed to room air (RA) or CIH for 35–50 days (n= 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (−200 μm to +200 μm relative to caudal end of area postrema;n= 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of −800, −400, 0, +400, and +800 μm relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH1) HR responses to microinjection of AMPA into the left NA were reduced (RA −290 ± 30 vs. CIH −227 ± 15 beats/min,P< 0.05);2) HR responses to microinjection of NMDA into the left NA were reduced (RA −302 ± 16 vs. CIH −238 ± 27 beats/min,P< 0.05); and3) the number of NMDAR1, AMPA GluR1, and AMPA GluR2/3-immunoreactive cells in the NA was reduced (P< 0.05). These results suggest that degeneration of NA neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH.
