Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis.
Norepinephrine deficiency with normal blood pressure control in congenital insensitivity to pain with anhidrosis.
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DOI：
10.1002/ana.24377
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发表时间：
2015-05
影响因子：
11.2
通讯作者：
Kaufmann, Horacio
中科院分区：
文献类型：
--
作者：
Norcliffe-Kaufmann, Lucy;Katz, Stuart D.;Axelrod, Felicia;Kaufmann, Horacio
先天性无痛无汗症（CIPA）是由NKTR1基因突变引起的。这会影响皮肤中神经生长因子（NGF）依赖性神经元（包括交感胆碱能神经元）的发育，导致无汗症。心血管和血压调节似乎正常，但交感肾上腺素能神经元的完整性尚未得到测试。我们研究了14例CIPA患者，10例慢性交感神经活性不足（纯自主神经功能衰竭）患者和15例正常年龄匹配的对照组的血压，心率，血浆中的儿茶酚胺，血管加压素，内皮素和肾素活性浓度的影响。在所有14例CIPA患者中，血浆去甲肾上腺素水平非常低或检测不到，直立时未增加，但直立血压保持良好。血浆肾上腺素水平正常，直立时升高。血浆肾素活性也适当增加时直立和呋塞米诱导的容量不足。一氧化氮介导的内皮功能是完整的。单纯自主神经功能衰竭患者在仰卧位和直立位的血浆去甲肾上腺素水平也非常低，但与CIPA患者相反，他们无法维持直立位的血压。结果表明，节后交感神经元在CIPA严重亏损，但肾上腺髓质的嗜铬细胞幸免。这证实了NGF信号传导对交感神经和嗜铬细胞发育的不同影响。CIPA患者站立时血压保持良好的发现挑战了目前去甲肾上腺素在动脉压调节中作用的概念。
Congenital insensitivity to pain with anhidrosis (CIPA) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested. We examined the effect of posture on blood pressure, heart rate, plasma concentration of catecholamines, vasopressin, endothelin and renin activity in 14 patients with CIPA, 10 patients with chronically deficient sympathetic activity (pure autonomic failure) and 15 normal age-matched controls. In all 14 patients with CIPA plasma norepinephrine levels were very low or undetectable and failed to increase when upright, yet upright blood pressure was well maintained. Plasma epinephrine levels were normal and increased upright. Plasma renin activity also increased appropriately when upright and after furosemide-induced volume depletion. Nitric oxide-mediated endothelial function was intact. Patients with pure autonomic failure also had very low levels of plasma norepinephrine both supine and upright, but in contrast to patients with CIPA failed to maintain blood pressure upright. The results indicate that post-ganglionic sympathetic neurons are severely depleted in CIPA, but chromaffin cells of the adrenal medulla are spared. This confirms the differential effect of NGF signaling for sympathetic neural and chromaffin cell development. The finding that patients with CIPA maintain blood pressure well on standing challenges current concepts of the role of norepinephrine in the regulation of arterial pressure.
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影响因子：
8.3
作者：
Harris, Ryan A.;Nishiyama, Steven K.;Richardson, Russell S.
通讯作者：
Richardson, Russell S.
影响因子：
37.8
作者：
Guzzetti, S;Borroni, E;Porta, A
通讯作者：
Porta, A
DOI：
10.1073/pnas.1308596110
发表时间：
2013-11-12
影响因子：
11.1
作者：
George, Lynn;Chaverra, Marta;Lefcort, Frances
通讯作者：
Lefcort, Frances
影响因子：
--
作者：
Cygankiewicz, Iwona;Zareba, Wojciech
通讯作者：
Zareba, Wojciech
影响因子：
3.3
作者：
Barbe, P;Galitzky, J;Berlan, M
通讯作者：
Berlan, M