The neurogenic vasodilator response to endothelin-1:: a study in human skin in vivo
The neurogenic vasodilator response to endothelin-1:: a study in human skin in vivo
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DOI：
10.1017/s0958067000020893
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发表时间：
2000-11-01
影响因子：
2.7
通讯作者：
Clough, GF
中科院分区：
文献类型：
--
作者：
Katugampola, R;Church, MK;Clough, GF
我们已经调查了潜在的介质和机制的有效的血管活性肽，内皮素-1（ET-1）及其异构体ET-2和ET-3在人体皮肤中的血管舒张作用，在体内，使用皮肤微透析定量释放介质内的真皮反应和扫描激光多普勒成像测量血流量的变化。观察局部麻醉、L-NAME抑制一氧化氮合酶（NOS）和阻断ET受体对ET诱导的血管反应的影响。ET-1、ET-2和ET-3均引起剂量依赖性苍白区，周围有持续时间较长的潮红，伴有短暂的烧灼性瘙痒。在对5 μ M ET-1的苍白反应内收集的透析液中的一氧化氮（NO）浓度（1.43 +/- 0.64 μ M，n = 5）与注射前收集的基线水平无显著差异（0.86 ± 0.38 μ M），而在耀斑中的增加在皮内注射后4 - 10分钟达到峰值2.28 ± 0.61 μ M（P < 0.004）。局麻药预处理可减缓闪光的发展，并在注射后20 min显著减小其大小，最多可达52%（P < 0.05），但对中心苍白无显著影响。经透析给予L-NAME也可显著减少ET-1引起的发作（P < 0.005）。波生坦是一种非选择性的ETA/ETB拮抗剂，当在注射部位通过透析给药时，ET-1诱导的苍白和周围闪光的面积分别减少了41%和26%。在对ET-1、ET-2或ET-3的苍白或潮红反应中，未测得组织组胺显著增加。总之，这些数据证实，血管舒张反应内皮素-1在人体皮肤是神经源性的起源，它是由一氧化氮的局部释放介导的一部分。似乎很少有证据表明肥大细胞衍生的组胺参与ET诱导的血管舒张的启动或调节。
We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 muM ET-1 (1.43 +/- 0.64 muM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 muM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 muM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ETA/ETB antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced palter and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.