Lin H C, Kang B H, Wan F J, Huang S T, Tseng C J
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
Eur J Pharmacol. 2000 Oct 27;407(1-2):83-9. doi: 10.1016/s0014-2999(00)00684-1.
Nitric oxide (NO) and glutamate are both important mediators of the central cardiovascular regulation in the nucleus tractus solitarii. Our previous studies revealed that the central cardiovascular effects of NO in the nucleus tractus solitarii could be inhibited by glutamate receptor blockade. On the other hand, nitric oxide synthase (NOS) inhibitor attenuated the cardiovascular effects of glutamate. Thus, NO and glutamatergic systems appear to interact in central cardiovascular regulation. The present study examined whether NO and glutamate may affect each other's release/production in the nucleus tractus solitarii. A microdialysis probe was implanted into the nucleus tractus solitarii of male Sprague-Dawley rats, and the changes in the extracellular levels of glutamate and NO were determined by high performance liquid chromatography coupled with electrochemical detection and an NO analyzer, respectively. The results showed that NO solution elicited >10 fold increases in the extracellular level of glutamate, which returned to normal 60 min after the end of NO perfusion. The NO donor N-acetyl-penicillamine (SNAP) had an effect similar to NO solution. Furthermore, the glutamate level was reduced to 61% of basal value by perfusion with the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). When glutamate receptor agonist N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methylixoxazole-4-propionic acid (AMPA) was administered into the nucleus tractus solitarii, the extracellular NO level was increased by 70-100%, whereas glutamate receptor antagonists (MK-801 hydrogen maleate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) did not alter the basal levels of NO. These results suggest that NO and glutamate may enhance each other's release/production in the nucleus tractus solitarii. This reciprocal regulation of NO and glutamate may be important in central cardiovascular control in the nucleus tractus solitarii.
一氧化氮（NO）和谷氨酸都是孤束核中中枢心血管调节的重要介质。我们之前的研究表明，孤束核中NO的中枢心血管效应可被谷氨酸受体阻断所抑制。另一方面，一氧化氮合酶（NOS）抑制剂可减弱谷氨酸的心血管效应。因此，NO和谷氨酸能系统在中枢心血管调节中似乎相互作用。本研究检测了NO和谷氨酸是否会相互影响彼此在孤束核中的释放/产生。将微透析探针植入雄性Sprague-Dawley大鼠的孤束核，分别通过高效液相色谱结合电化学检测和NO分析仪测定谷氨酸和NO的细胞外水平变化。结果显示，NO溶液使谷氨酸的细胞外水平升高了10倍以上，在NO灌注结束后60分钟恢复正常。NO供体N-乙酰青霉胺（SNAP）具有与NO溶液相似的作用。此外，用NOS抑制剂N（G）-单甲基-L-精氨酸（L-NMMA）灌注可使谷氨酸水平降至基础值的61%。当将谷氨酸受体激动剂N-甲基-D-天冬氨酸（NMDA）或α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）注入孤束核时，细胞外NO水平升高70-100%，而谷氨酸受体拮抗剂（马来酸氢MK-801和6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX））并未改变NO的基础水平。这些结果表明，NO和谷氨酸可能在孤束核中相互增强彼此的释放/产生。NO和谷氨酸的这种相互调节可能在孤束核的中枢心血管控制中起重要作用。
