Zhou Wei, Fu Liang-Wu, Tjen-A-Looi Stephanie C, Guo Zhi-ling, Longhurst John C
Susan Samueli Center for Integrative Medicine, Department of Medicine, School of Medicine, University of California, Irvine, CA 92697-4075, USA.
Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1309-18. doi: 10.1152/ajpheart.00202.2006. Epub 2006 Apr 21.
The rostral ventrolateral medulla (rVLM) is involved in processing visceral sympathetic reflexes. However, there is little information on specific neurotransmitters in this brain stem region involved in this reflex. The present study investigated the importance of glutamate and glutamatergic receptors in the rVLM during gallbladder stimulation with bradykinin (BK), because glutamate is thought to function as an excitatory neurotransmitter in this region. Stimulation of visceral afferents activated glutamatergic neurons in the rVLM, as noted by double-labeling with c-Fos and the cellular vesicular glutamate transporter 3 (VGLUT3). Visceral reflex activation significantly increased arterial blood pressure as well as extracellular glutamate concentrations in the rVLM as determined by microdialysis. Barodenervation did not alter the release of glutamate in the rVLM evoked by visceral reflex stimulation. Iontophoresis of glutamate into the rVLM enhanced the activity of sympathetic premotor cardiovascular rVLM neurons. Also, the responses of these neurons to visceral afferent stimulation with BK were attenuated significantly (70%) by blockade of glutamatergic receptors with kynurenic acid. Microinjection of either an N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanate (25 mM, 30 nl) or an dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (2 mM, 30 nl) into the rVLM significantly attenuated the visceral sympathoexcitatory reflex responses. These results suggest that glutamate in the rVLM serves as an excitatory neurotransmitter through a baroreflex-independent mechanism and that both NMDA and AMPA receptors mediate the visceral sympathoexcitatory reflex responses.
延髓头端腹外侧区（rVLM）参与内脏交感反射的处理。然而，关于该脑干区域参与此反射的特定神经递质的信息却很少。本研究探讨了在用缓激肽（BK）刺激胆囊期间，谷氨酸和谷氨酸能受体在rVLM中的重要性，因为谷氨酸被认为在该区域起兴奋性神经递质的作用。如通过c-Fos与细胞囊泡谷氨酸转运体3（VGLUT3）双重标记所示，内脏传入神经的刺激激活了rVLM中的谷氨酸能神经元。通过微透析测定，内脏反射激活显著增加了动脉血压以及rVLM中的细胞外谷氨酸浓度。去压力神经支配并未改变内脏反射刺激所诱发的rVLM中谷氨酸的释放。将谷氨酸离子导入rVLM增强了交感运动前心血管rVLM神经元的活性。此外，用犬尿氨酸阻断谷氨酸能受体后，这些神经元对BK内脏传入刺激的反应显著减弱（70%）。向rVLM中微量注射N-甲基-D-天冬氨酸（NMDA）受体拮抗剂2-氨基-5-膦酰基戊酸（25 mM，30 nl）或α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（2 mM，30 nl），均显著减弱了内脏交感兴奋反射反应。这些结果表明，rVLM中的谷氨酸通过一种不依赖压力反射的机制起兴奋性神经递质的作用，并且NMDA和AMPA受体均介导内脏交感兴奋反射反应。
