Contribution of Nerve Growth Factor to The Increased Sympathetic Nerve Activity in Hypertension

神经生长因子对高血压交感神经活动增加的贡献

基本信息

批准号：
04670551
负责人：
HANO Takuzo
金额：
$ 1.34万
依托单位：
WAKAYAMA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

Increased sympathetic nervous activity has been demonstrated in spontaneously hypertensive rats(SHR) and human essential hypertension. Especially, in SHR, increased sympathetic nerve innervation and enhanced norepinephrine(NE) release from vascular tissue have been reported, precise mechanisms of which are not clearly known. To elucidate the contribution of Nerve growth factor(NGF) to the increased sympathetic nervous activity in SHR, the secretion of NGF from cultured vascular smooth muscle cells(VSMCs) was examined and NGF content in various tissues from SHR and control Wistar-Kyoto rats(WKY) was measured. The effects of NGF on NE release from the sympathetic nerve endings were also examined. NGF was purified from mouse submandibular gland according to the Bocchini's method. VSMCs were obtained from the aorta of WKY by explant method. NGF activity was measured by bioassay and NGF content was measured by enzyme immunoassay. Effects of NGF on NE overflow to electrical stimulation were examined using perfused mesenteric artery preparation. 1) Conditioned medium prepared from VSMCs had neurite extention effects on sensory and sympathetic neurons and this effect was blocked by anti-NGF serum. 2) At 3 weeks of age, SHR had a greater NGF content in the spleen, the sciatic nerve, and the mesenteric artery in comparison with WKY.However, these differences were not observed in the adults animals. 3) The expression of NGFmRNA was increased in media of mesenteric artery in in situ hybridization. 4) NGF secretion from cultured VSMCs and mesenteric artery and aorta segment was not significantly difference in in situ hybridization. 5) NGF inhibited NE overflow to electrical stimulation from sympathetic nerve endings in a dose-dependent manner. Inhibition of NE overflow also occurred in the presence of a neuronal uptake blocker, desipramine(5x10-8M). 6) Neuromodulatory effect of NGF was attenuated in 4 week old SHR.However, there were no significant differences between 12 week o

在自发性高血压大鼠（SHR）和人类原发性高血压中已证实交感神经活动增加。特别是，在 SHR 中，已报道交感神经支配增加和血管组织去甲肾上腺素 (NE) 释放增加，但其确切机制尚不清楚。为了阐明神经生长因子（NGF）对 SHR 交感神经活性增加的贡献，检测了培养的血管平滑肌细胞（VSMC）中 NGF 的分泌，以及 SHR 和对照 Wistar-Kyoto 大鼠各组织中 NGF 的含量。 WKY) 进行了测量。还检查了 NGF 对交感神经末梢释放 NE 的影响。根据Bocchini方法从小鼠颌下腺中纯化NGF。通过外植体法从WKY的主动脉中获得VSMCs。通过生物测定法测定NGF活性，通过酶免疫测定法测定NGF含量。使用灌注肠系膜动脉制剂检查 NGF 对电刺激 NE 溢出的影响。 1)由VSMC制备的条件培养基对感觉神经元和交感神经元具有神经突延伸作用，并且该作用被抗NGF血清阻断。 2）3周龄时，与WKY相比，SHR的脾脏、坐骨神经和肠系膜动脉中的NGF含量更高。然而，在成年动物中没有观察到这些差异。 3)原位杂交显示肠系膜动脉中层NGFmRNA表达增加。 4)原位杂交培养的VSMCs及肠系膜动脉和主动脉段NGF分泌量无显着差异。 5)NGF以剂量依赖性方式抑制交感神经末梢电刺激的NE溢出。在存在神经元摄取阻滞剂地昔帕明 (5x10-8M) 的情况下也会抑制 NE 溢出。 6) NGF的神经调节作用在4周龄SHR中减弱。然而，与12周龄和12周龄SHR之间没有显着差异。