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PHARMACOLOGICAL ANALYSIS OF NEURO-IMMUNO-ENDOCRINE AXIS-CENTRAL INTERLEUKIN-1 beta ON SYMPATHETIC NERVOUS SYSTEM-

神经-免疫-内分泌轴-中枢白细胞介素-1β对交感神经系统的药理学分析-

基本信息

批准号：
08670115
负责人：
OSUMI Yoshitsugu
金额：
$ 1.34万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Excitatory mechanisms of central sympathetic outflow by interleukin-1 beta (IL-1 beta) was investigated in urethane-anesthetized rats. intracerebroventricular administration of IL-1 beta (50-200ng/animal) elevated plasma levels of noradrenaline (NA), while those of adrenaline (Ad) were not affected. This IL-1 beta-induced elevation of NA was abolished by chemical sympathectomy, indomethacin (i.c.v.), L-N^G-nitroarginine methyl ester (i.c.v.), a nitric oxide synthase inhibitor and oxyhemoglobin (i.c.v.), a nitric oxide scavenger. D-Isomer of L-N^G-nitroarginine and methemoglobin were without effect.Then, in the next series, roles of nitric oxide in the central excitatory mechanisms of sympatho-adrenomedullarly outflow were examined. Intracerebroventricular administration of 3-morpholinosydnominine (SIN-1), a nitric oxide doner, dose-dependently (100-500ug/animal) elevated plasma Ad and NA levels. The elevation of Ad was much more marked than that of NA.These elevations were abolished by indomethacin and carboxy-PTIO,a nitric oxide scavenger. Furthermore, the elevation of Ad levels was abolished by thromboxane A2 synthase inhibitors (furegrelate and carboxyheptyl imidazole), and also by thromboxane A2 receptor blockers ({+}-S-145 and SQ29548), while the elevation of NA was anaffected by any of these test agents.{Conclusion} : (1) Nitric oxide mediates the IL-1beta-induced central activation of sympathetic outflow. (2) Thromboxane A2 is probably involved in the nitric oxide-induced central activation of adrenomedullary outflow.

在麻醉大鼠中研究了白细胞介素-1 β（IL-1 β）对中枢交感神经流出的兴奋机制。侧脑室注射IL-1 β（50- 200 ng/只）使血浆去甲肾上腺素（NA）水平升高，而肾上腺素（Ad）水平无明显变化。这种IL-1 β诱导的NA升高被化学交感神经切除术、吲哚美辛（i. c. v.）L-N-硝基精氨酸甲酯（i. c. v.），一氧化氮合酶抑制剂和氧合血红蛋白（i. c. v.），一氧化氮清除剂L-N、G-硝基精氨酸D-异构体和高铁血红蛋白无影响。接下来，我们研究了一氧化氮在交感-肾上腺髓质流出的中枢兴奋机制中的作用。侧脑室注射一氧化氮供体3-吗啉代去甲肾上腺素（SIN-1），剂量依赖性地（100- 500 μ g/只）升高血浆Ad和NA水平。Ad的升高比NA明显得多，这些升高可被消炎痛和一氧化氮清除剂carboxy-PTIO消除。此外，血栓素A2合成酶抑制剂（呋替酯和羧庚基咪唑）和血栓素A2受体阻断剂（{+}-S-145和SQ 29548）可消除Ad水平的升高，而NA水平的升高则不受任何这些试验药物的影响。结论：（1）一氧化氮介导了IL-1 β诱导的交感神经兴奋。(2)血栓素A2可能参与一氧化氮诱导的肾上腺髓质流出的中枢激活。