Skin blood flow after transdermal S-nitrosothio-acetylglucose
Skin blood flow after transdermal S-nitrosothio-acetylglucose
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DOI：
10.1016/s0140-6736(05)64133-5
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发表时间：
1997-08-09
期刊：
影响因子：
168.9
通讯作者：
Belch, JJF
中科院分区：
文献类型：
--
作者：
Khan, F;Greig, IR;Belch, JJF
一氧化氮（NO）在皮肤微血管中的作用尚不清楚，因为ng -单甲基- l-精氨酸（L-NMMA）对皮肤血流的影响是可变的。虽然80-90%的皮肤血流量具有体温调节功能，但它是临床上重要的营养成分。硝基血管扩张剂，如硝普钠和三硝酸甘油，很难在皮肤微血管中进行研究，因为它们在释放一氧化氮之前需要广泛的代谢。s -亚硝基硫醇释放一氧化氮，在动物中是血管扩张剂。s -亚硝基硫代乙酰葡萄糖（SNAG）在离体大鼠尾动脉中具有血管舒张作用。我们现在研究经皮应用SNAG对人体皮肤微血管的影响。采用激光多普勒成像和光导分光光度法分别测量皮肤灌注和皮肤氧合。研究对象为6名健康男性，平均年龄29.7岁，年龄范围25-41岁。经皮SNAG在前臂掌侧和手指背侧进行评估，这些区域的灌注主要起营养作用，而在指髓处则有大量的热调节分流。前臂连接一个2厘米的圆形孔，手指连接一个1厘米的孔。SNAG在50:50的乙醇水溶液中溶解，得到0.5%、0.5%和1.5%的浓度。在前臂的不同部位和不同手指上随机测试每种浓度。SNAG使前臂（p< 0.01，方差分析）和指背（p< 0.005，方差分析）的皮肤灌注显著增加，但指髓没有增加（图）。氧饱和度仅在前臂升高（p< 0.001，方差分析）。我们已经证明，使用不需要代谢转化的新的NO供体，营养皮肤微血管对外源性NO有反应，而温度调节区域相对不敏感。这与L-NMMA显著降低手指背和前臂基底皮肤灌注的发现是一致的，并且NO在人体皮肤血流量的热调节控制中没有主要作用。SNAG与其他硝基血管扩张剂相比具有优势，因为在溶液中，它能迅速释放NO并形成醋酸硫葡萄糖的惰性二硫化物。目前还不清楚
The role of nitric oxide (NO) in skin microvessels is unclear because of the variable effects of NG-monomethyl-L-arginine (L-NMMA) on skin blood flow. 1, 2 Although 80–90% of skin blood flow serves a thermoregulatory function, it is the nutritional component that is clinically important. Nitrovasodilators, such as sodium nitroprusside and glyceryl trinitrate, are difficult to study in cutaneous microvessels because they require extensive metabolism before they release NO. S-nitrosothiols release NO and are vasodilators in animals. 3 S-nitrosothio-acetylglucose (SNAG) acts as a vasodilator in the isolated rat tail artery. 4 We now examine the effects of transdermal application of SNAG on human skin microvessels. We measured skin perfusion with laser doppler imaging and skin oxygenation by lightguide spectrophotometry. Six healthy men (mean age 29· 7 years, range 25–41) were studied. Transdermal SNAG was assessed on the volar forearm and dorsum of the finger, areas where perfusion serves mainly a nutritive role, and at the finger pulp where thermoregulatory shunts are abundant. A 2 cm circular well was attached to the forearm and a 1 cm well was used for the finger. SNAG was dissolved in 50: 50 aqueous ethanol to give 0· 5, 1· 0, and 1· 5% concentrations. Each concentration was tested randomly at different sites on the forearm and on different fingers. SNAG produced significant increases in skin perfusion at the forearm (p< 0· 01, ANOVA) and dorsum of the finger (p< 0· 005, ANOVA), but not at the pulp of the finger (figure). Oxygenation saturation increased at the forearm only (p< 0· 001, ANOVA).We have shown, using a new NO donor that requires no metabolic conversion, that nutritional skin microvessels are responsive to exogenous NO whereas thermoregulatory areas are relatively insensitive. This is consistent with the findings that L-NMMA significantly reduces basal skin perfusion at both the dorsum of the finger and the forearm, and that NO serves no major role in the thermoregulatory control of skin blood flow in people. 1 SNAG has advantages over other nitrovasodilators because, in solution, it rapidly releases NO and forms the inert disulphide of thioglucose acetate. It is not clear