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非NMDA和NMDA受体在谷氨酸诱导的脑桥和延髓升压或降压反应中的作用。

Involvement of non-NMDA and NMDA receptors in glutamate-induced pressor or depressor responses of the pons and medulla.

作者信息

Chen S Y, Wu W C, Tseng C J, Kuo J S, Chai C Y

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

出版信息

Clin Exp Pharmacol Physiol. 1997 Jan;24(1):46-56. doi: 10.1111/j.1440-1681.1997.tb01782.x.

Abstract
  1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50-100 nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50-100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50-100 nL) and AMPA (0.2 mmol/L, 50-100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain.
摘要
  1. 选用55只未做处理的猫和6只压力感受器去神经及迷走神经切断的猫(雌雄不限),腹腔注射氨基甲酸乙酯(400毫克/千克)和α-氯醛糖(40毫克/千克)进行麻醉。记录全身动脉压(SAP)、平均全身动脉压(MSAP)、交感神经椎动脉神经(VNA)和肾神经活动(RNA)的反应。2. 在未做处理的动物中,将L-谷氨酸单钠(Glu,0.1摩尔/升,50纳升)微量注射到蓝斑(LC)、巨细胞被盖区(GTF)、延髓头端腹外侧区(RVLM)和延髓背内侧区(DM)的升压区,以及延髓尾端腹外侧区(CVLM)的降压区。在微量注射谷氨酸拮抗剂、谷氨酸二乙酯(GDEE,0.5摩尔/升,50 - 100纳升,一种竞争性AMPA受体阻滞剂)或2-氨基-5-磷酸戊酸(D-AP5,0.025摩尔/升,50 - 100纳升,一种竞争性N-甲基-D-天冬氨酸(NMDA)受体阻滞剂)之前和之后,比较所诱导的作用。GDEE完全阻断了所有升压区引起的SAP和VNA的升高。D-AP5仅部分阻断了升压作用,但轻微阻断了来自LC、GTF和DM,特别是来自RVLM的VNA和RNA反应。GDEE和D-AP5均未阻断CVLM引起的SAP降压反应和两种神经活动。3. 在压力感受器去神经的动物中,将NMDA(2毫摩尔/升,50 - 100纳升)和AMPA(0.2毫摩尔/升,50 - 100纳升)微量注射到GTF、RVLM和DM的相同升压区以及对Glu激活(0.1摩尔/升,30纳升)有反应的CVLM降压区。在RVLM、DM和CVLM中,NMDA或AMPA的结果与Glu诱导的结果相似。然而,在GTF中,微量注射NMDA或AMPA并未诱导出与Glu相似的反应。这表明GTF的性质可能与RVLM和DM不同。4. 上述结果表明,Glu从LC、GTF、DM尤其是RVLM诱导的升压反应主要通过AMPA受体介导。Glu从CVLM诱导的降压反应可能并非主要由AMPA或NMDA受体介导。5. 在压力感受器完整和去神经的猫中,刺激升压区通常会导致VNA升高和RNA降低,而在降压区CVLM中,VNA和RNA均降低。VNA而非RNA与升压反应呈正相关,而VNA和RNA均与降压反应呈正相关。这可能表明交感神经椎动脉和肾神经的神经元在大脑中是按拓扑结构组织的。

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