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

自发性高血压大鼠（SHR）和人类基本高血压已经证明了交感神经活动的增加。尤其是在SHR中，已经报道了同情神经神经支配和增强的去甲肾上腺素（NE）从血管组织中释放出来，这些机制的精确机制尚不清楚。为了阐明神经生长因子（NGF）对SHR交感神经活动的增加的贡献，测量了NGF的分泌NGF从培养的血管平滑肌细胞（VSMC）分泌，并测量了SHR和对照Wistar-kyoto大鼠（WKY）的各种组织中的NGF含量。还检查了NGF对NE释放的影响。根据Bocchini的方法从小鼠下颌腺纯化NGF。通过Explant方法从WKY的主动脉获得VSMC。通过生物测定测量NGF活性，并通过酶免疫测定法测量NGF含量。使用灌注肠系膜动脉制备检查NGF对NE溢流到电刺激的影响。 1）由VSMC制备的条件培养基对感觉和交感神经元具有神经突的效果，并且这种作用被抗NGF血清阻断。 2）在3周龄时，SHR在脾脏，坐骨神经和肠系膜动脉中具有更大的NGF含量，与WKY相比，在成年动物中未观察到这些差异。 3）在原位杂交中，肠系膜动脉培养基中NGFMRNA的表达增加。 4）在原位杂交中，培养的VSMC和肠系膜动脉和主动脉段的NGF分泌没有显着差异。 5）NGF以剂量依赖性的方式抑制了NE溢出到来自交感神经末端的电刺激。在存在神经元摄取阻滞剂（5x10-8m）存在下，NE溢出的抑制也发生。 6）NGF的神经调节作用在4周大的SHR中衰减。但是，12周O之间没有显着差异