Shiseido Research Center, Yokohama, Japan.
J Invest Dermatol. 2010 Apr;130(4):1158-66. doi: 10.1038/jid.2009.350. Epub 2009 Nov 26.
The source of nitric oxide (NO) in the cutaneous circulation remains controversial. We hypothesized that epidermis might generate NO in response to mechanical stimulation. In hairless mouse (HR-1) skin organ culture, mechanical stimulation resulted in NO release, which declined within 30 minutes after cessation. A similar NO release occurred in a reconstructed skin model containing only keratinocytes and fibroblasts and was suppressed after detachment of the epidermal layer. Moreover, the stimulation-induced NO release was significantly lower in skin organ culture from neuronal NO synthase knockout (nNOS-KO) mice, compared with wild-type (WT) mice. Mechanical stimulation of skin organ cultures from HR-1, nNOS-KO, endothelial NOS-KO (eNOS-KO), and WT mice caused an enlargement of cutaneous lymphatic vessels. The enlargement was significantly lower after detachment of the epidermal layer than in normal skin samples and was significantly lower for nNOS-KO than for WT mice. Skin blood flow in nNOS-KO mice after stimulation was significantly lower than in WT mice. eNOS-KO mice also showed lower responses than WT mice, and the difference was similar to that in the case of nNOS-KO mice. These results are consistent with the idea that NO generated by epidermal nNOS has a significant role in the cutaneous circulatory response to mechanical stimulation.
一氧化氮（NO）在皮肤循环中的来源仍存在争议。我们假设表皮可能会对机械刺激产生 NO。在无毛小鼠（HR-1）皮肤器官培养中，机械刺激导致 NO 释放，停止刺激后 30 分钟内 NO 释放减少。在仅包含角质形成细胞和成纤维细胞的重建皮肤模型中也发生了类似的 NO 释放，并且在去除表皮层后被抑制。此外，与野生型（WT）小鼠相比，神经元型一氧化氮合酶敲除（nNOS-KO）小鼠皮肤器官培养物中的刺激诱导的 NO 释放明显降低。HR-1、nNOS-KO、内皮型一氧化氮合酶敲除（eNOS-KO）和 WT 小鼠皮肤器官培养物的机械刺激导致皮肤淋巴管扩张。去除表皮层后的扩张明显低于正常皮肤样本，nNOS-KO 比 WT 小鼠的扩张明显降低。刺激后 nNOS-KO 小鼠的皮肤血流量明显低于 WT 小鼠。eNOS-KO 小鼠的反应也低于 WT 小鼠，差异与 nNOS-KO 小鼠相似。这些结果与表皮 nNOS 产生的 NO 在机械刺激引起的皮肤循环反应中具有重要作用的观点一致。
