Christen Samuel, Delachaux Anne, Dischl Benoît, Golay Sandrine, Liaudet Lucas, Feihl François, Waeber Bernard
Division of Clinical Pathophysiology, University Hospital, Lausanne, Switzerland.
J Cardiovasc Pharmacol. 2004 Dec;44(6):659-64. doi: 10.1097/00005344-200412000-00006.
The assessment of the skin microvasculature response to iontophoretically applied acetylcholine (ACh) and local warming makes it possible to explore noninvasively in humans the functional integrity of endothelium. The present study aimed to examine whether these two stimuli of nitric oxide (NO) release have a dose-dependent vasorelaxant activity. For this purpose we assessed in healthy subjects using a laser-Doppler imaging system the increase in forearm blood flow following transdermal application of increasing amounts of ACh [with an iontophoretic current of either 0.28 mC/cm2 (n = 18), 0.56 mC/cm2 (n = 14), 1.4 mC/cm2 (n = 26), 7 mC/cm2 (n = 14), 28 mC/cm2 (n = 14), or 48 mC/cm2 (n = 6)] or graded warming of the skin [to either 37 degrees C (n = 8), 39 degrees C (n = 4) or 41 degrees C (n = 12)]. The maximal vasodilation was significantly smaller with the lowest dose than with the higher doses of ACh, and a plateau was reached with the 1.4 mC/cm2 dose. The skin blood flow responses to ACh were not dependent on the pulsed or continuous pattern of iontophoretic administration. The hyperemia induced by the local heating to 41 degrees C was significantly greater than that observed with the other temperatures. When measured in the same subjects, the magnitude of the maximal ACh-mediated skin blood flow increase was significantly smaller than the vasodilation associated with the warming to 41 degrees C. In summary, transdermally applied ACh and local heating of the skin induce a dose-dependent vasorelaxation. These techniques represent a unique means to investigate noninvasively the functional vasodilatory capacity of the skin microvasculature.
评估皮肤微血管对离子电渗法施加的乙酰胆碱（ACh）和局部升温的反应，使得在人体中无创地探究内皮功能完整性成为可能。本研究旨在检验这两种一氧化氮（NO）释放刺激是否具有剂量依赖性血管舒张活性。为此，我们使用激光多普勒成像系统评估了健康受试者在经皮施加不同剂量ACh[离子电渗电流分别为0.28 mC/cm²（n = 18）、0.56 mC/cm²（n = 14）、1.4 mC/cm²（n = 26）、7 mC/cm²（n = 14）、28 mC/cm²（n = 14）或48 mC/cm²（n = 6）]或皮肤分级升温[至37℃（n = 8）、39℃（n = 4）或41℃（n = 12）]后前臂血流量的增加情况。最低剂量的ACh引起的最大血管舒张明显小于较高剂量，且在1.4 mC/cm²剂量时达到平台期。皮肤对ACh的血流反应不依赖于离子电渗给药的脉冲或连续模式。局部加热至41℃引起的充血明显大于其他温度时观察到的值。在同一受试者中测量时，最大ACh介导的皮肤血流增加幅度明显小于与升温至41℃相关的血管舒张。总之，经皮应用ACh和皮肤局部加热可诱导剂量依赖性血管舒张。这些技术是无创研究皮肤微血管功能舒张能力的独特手段。
