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

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。

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.