Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways
Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways
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DOI：
10.1210/jc.2003-030377
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发表时间：
2003-11-01
影响因子：
5.8
通讯作者：
Wright, IMR
中科院分区：
文献类型：
--
作者：
Crompton, R;Clifton, VL;Wright, IMR
CRH作为下丘脑-垂体-肾上腺轴和应激反应的介导者发挥核心作用，并且是有效的血管扩张剂。以前，我们已经表明，CRH导致人类皮肤的性别特异性血管舒张，尽管CRH的运作机制尚不清楚。CRH引起大鼠皮肤肥大细胞脱颗粒。因此，组胺和其他肥大细胞衍生的因子可能是间接负责CRH的血管舒张作用，虽然CRH也被称为直接作用于vascularis. CRH诱导的血管舒张在人体皮肤中使用激光多普勒血流仪和离子电渗在成年女性。CRH（1 nM）的前臂离子电渗给药，并同时在同一地区的激光多普勒测量血流量。在肥大细胞脱粒抑制剂色甘酸钠、组胺H（1）拮抗剂异丙嗪或H（2）拮抗剂雷尼替丁存在下，CRH诱导的皮肤微血管扩张显著减少。CRH诱导的扩张也显着减少的存在下，一氧化氮合酶抑制剂，N（ω）-硝基-L-精氨酸甲酯，或环氧合酶抑制剂，piroxicam.These研究结果提供了新的证据表明，CRH诱导的血管舒张在人体皮肤发生通过肥大细胞脱粒，主要是由组胺介导，并在较小程度上，由前列环素和一氧化氮。
CRH plays a central role as a mediator of the hypothalamic-pituitary-adrenal axis and stress response and is a potent vasodilator. Previously, we have shown that CRH causes a gender-specific vasodilation in human skin, although the mechanism by which CRH operates is unclear. CRH causes mast cell degranulation in rat skin. As such, histamine and other mast cell-derived factors may be indirectly responsible for the vasodilatory effects of CRH, although CRH is also known to act directly on the vasculature.CRH-induced vasodilation in human skin was examined using laser Doppler flowmetry and iontophoresis in adult females. CRH (1 nM) was administered iontophoretically to the forearm, and blood flow was measured simultaneously in the same area by laser Doppler. CRH-induced dilation of the skin microvasculature was significantly reduced in the presence of the mast cell degranulation inhibitor, sodium cromoglycate, the histamine H(1)-antagonist, promethazine, or the H(2)-antagonist, ranitidine. CRH-induced dilation was also significantly reduced in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor, piroxicam.These findings provide novel evidence that CRH-induced vasodilation in human skin occurs via mast cell degranulation and is principally mediated by histamine and, to a lesser extent, by prostacyclin and nitric oxide.