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Roles of brain nitric oxide and prostaglandins in the regulation of central sympatho-adrenomedullary outflow in rats

脑一氧化氮和前列腺素在大鼠中枢交感肾上腺髓质流出调节中的作用

基本信息

批准号：
08672614
负责人：
YOKOTANI Kunihiko
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

We already reported that intracerebroventricularly (i.c.v.) administered interleukin-1beta (IL-1beta) inhibits vagally activated gastric acid secretion by activation of central prostaglandin (PG)-mediated sympathetic outflow (Eur.J.Pharmacol., 1995). I.c.v. administered PGE^2 also activates central sympathetic outflow through activation of brain EP3 receptors (Br.J.Pharmacol., 1995 ; 1996). In the present experiments, we examined possible roles of central nitric oxide (NO) in IL-1beta-mediated central activation of sympathetic outflow using male Wistar rats anesthetized with urethane. (1) I.c.v.administered IL-1beta elevated plasma noradrenaline (NA) levels. This IL-1beta-mediated response was abolished by i.c.v.administered 1-NAME (NO synthase inhibitor), oxyhemoglobin (NO scavenger), and indomethacin (cyclooxygenase inhibitor), (2) I.c.v.administered NO donors, sodium nitroprusside and 3-morpholinosydnonimine (SIN-1), inhibited vagally stimulated gastric acid secretion. This response was abolished by i.c.v.administered indomethacin, splanchnectomy and intramuscularly administered phentolamine, SIN-1 elevated plasma levels of adrenaline (Ad) and NA (Ad>>NA). SIN-1-mediated elevation of Ad and NA was abolished by intracerebroventricular pretreatment with indomethacin. On the other hand, intracerebroventricular pretreatment with thromboxane A2 synthase inhibitor, furegrelate, only abolished SIN-1-induced Ad elevation. These results indicate that central NO activates central sympatho-adrenomedullary system. I.c.v.administered IL-1beta activates central sympathetic outflow through NO-PG (E2) pathway and central thromboxane A2 activates central adrenomedullary pathways.

我们已经报道了脑室内（i. c. v.）施用的白细胞介素-1 β（IL-1 β）通过激活中枢前列腺素（PG）介导的交感神经流出来抑制迷走神经激活的胃酸分泌（Eur.J.Pharmacol.，1995年）。静脉注射PGE ^2还通过激活脑EP 3受体激活中枢交感神经流出（Br.J.Pharmacol.，1995 ; 1996）。在本实验中，我们使用乌拉坦麻醉的雄性Wistar大鼠研究了中枢一氧化氮（NO）在IL-1 β介导的交感神经流出中枢激活中的可能作用。(1)i. c. v.给予IL-1 β升高血浆去甲肾上腺素（NA）水平。静脉注射NO合成酶抑制剂1-NAME、NO清除剂氧合血红蛋白和环氧合酶抑制剂吲哚美辛可阻断IL-1 β介导的胃酸分泌。这种反应被i. c. v.给药吲哚美辛、内脏切除术和肌内给药酚妥拉明所消除，SIN-1升高血浆肾上腺素（Ad）和NA水平（Ad>>NA）。SIN-1介导的Ad和NA升高被吲哚美辛脑室内预处理所消除。另一方面，侧脑室预处理与血栓素A2合成酶抑制剂，furegrelate，只取消SIN-1诱导的Ad升高。这些结果表明，中枢NO激活中枢交感-肾上腺髓质系统。i. c. v.给药IL-1 β通过NO-PG（E2）途径激活中枢交感神经流出，中枢血栓素A2激活中枢肾上腺髓质途径。