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

研究了氨基甲酸乙酯麻醉大鼠中心性交感神经流出物中白细胞介素-1 β的兴奋机制。脑室内给予IL-1 β （50-200ng/只）可提高血浆去甲肾上腺素（NA）水平，而肾上腺素（Ad）水平不受影响。化学交感神经切除术、吲哚美辛（i.c.v）、L-N^ g -硝基精氨酸甲酯（i.c.v）（一种一氧化氮合酶抑制剂）和氧合血红蛋白（i.c.v）（一种一氧化氮清除剂）可消除IL-1 β诱导的NA升高。L-N^ g -硝基精氨酸和高铁血红蛋白的d -异构体无影响。然后，在接下来的系列中，研究了一氧化氮在交感神经-肾上腺髓质流出的中枢兴奋机制中的作用。脑室内给药3- morpholinosydopnomine (SIN-1)，一种一氧化氮供体，剂量依赖性（100-500ug/只）升高血浆Ad和NA水平。Ad的升高明显高于NA。这些升高被吲哚美辛和羧基ptio（一种一氧化氮清除剂）所消除。此外，血栓素A2合成酶抑制剂（fureglate和carboxyheptyl咪唑）和血栓素A2受体阻滞剂（{+}-S-145和SQ29548）均可消除Ad水平的升高，而NA的升高不受任何这些试验药物的影响。{结论}:(1)一氧化氮介导il -1 β诱导的交感神经流出的中枢激活。(2)血栓素A2可能参与了一氧化氮诱导的肾上腺髓质流出的中枢激活。

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.