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）给予白细胞介素-1 β (il -1 β)通过激活中央前列腺素（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)。静脉注射PGE^2也通过激活大脑EP3受体激活中枢交感神经流出（Br.J.Pharmacol）。， 1995年；1996)。在本实验中，我们用氨基甲酸乙酯麻醉雄性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的中枢激活中的可能作用。(1)给药il -1 β升高血浆去甲肾上腺素（NA）水平。这种il -1 - β介导的反应被灌注1-NAME （NO合成酶抑制剂）、氧合血红蛋白（NO清除剂）和吲哚美辛（环加氧酶抑制剂）所消除。(2)灌注NO供体、硝普钠和3- morpholinosydnon亚胺（sin1）抑制迷走神经刺激的胃酸分泌。这种反应被静脉注射吲哚美辛、切除内脏和肌注酚妥拉明所消除，血浆中肾上腺素（Ad）和NA （Ad>>NA）水平升高。脑室内吲哚美辛预处理可消除sin -1介导的Ad和NA升高。另一方面，使用血栓素A2合成酶抑制剂fureglate在脑室内预处理，仅能消除sin -1诱导的Ad升高。提示中枢NO激活中枢交感-肾上腺髓质系统。静脉注射il -1 β激活中枢交感神经通过NO-PG （E2）通路流出，中枢血栓素A2激活中枢肾上腺髓质通路。

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.