University of Dundee, School of Medicine, Dundee, Scotland, UK.
University of Dundee, School of Science and Engineering, Dundee, Scotland, UK.
Sci Rep. 2019 Jan 17;9(1):186. doi: 10.1038/s41598-018-36970-4.
Arterioles in the cutaneous microcirculation frequently display an oscillatory phenomenon defined vasomotion, consistent with periodic diameter variations in the micro-vessels associated with particular physiological or abnormal conditions. The cellular mechanisms underlying vasomotion and its physiological role have not been completely elucidated. Various mechanisms were demonstrated, based on cell Ca oscillations determined by the activity of channels in the plasma membrane or sarcoplasmic reticulum of vascular cells. However, the possible engagement in vasomotion of cell metabolic oscillations of mitochondrial or glycolytic origin has been poorly explored. Metabolic oscillations associated with the production of ATP energy were previously described in cells, while limited studies have investigated these fluctuations in-vivo. Here, we characterised a low-frequency metabolic oscillator (MO-1) in skin from live wild-type and Nrf2 mice, by combination of fluorescence spectroscopy and wavelet transform processing technique. Furthermore, the relationships between metabolic and microvascular oscillators were examined during phenylephrine-induced vasoconstriction. We found a significant interaction between MO-1 and the endothelial EDHF vasomotor mechanism that was reduced in the presence of oxidative stress (Nrf2 mice). Our findings suggest indirectly that metabolic oscillations may be involved in the mechanisms underlying endothelium-mediated skin vasomotion, which might be altered in the presence of metabolic disturbance.
皮肤微循环中的小动脉经常表现出一种振荡现象,称为血管运动,这与与特定生理或异常情况相关的微血管周期性直径变化一致。血管运动的细胞机制及其生理作用尚未完全阐明。基于血管细胞的质膜或肌浆网上通道的活性所确定的细胞 Ca 振荡,已经证明了各种机制。然而,细胞代谢振荡(线粒体或糖酵解来源)可能参与血管运动的情况,还没有得到充分的探索。先前在细胞中描述了与 ATP 能量产生相关的代谢振荡,而有限的研究调查了这些波动在体内的情况。在这里,我们通过荧光光谱和小波变换处理技术,对来自活体野生型和 Nrf2 小鼠的皮肤中的低频代谢振荡器 (MO-1) 进行了特征描述。此外,还在去甲肾上腺素诱导的血管收缩期间检查了代谢和微血管振荡器之间的关系。我们发现 MO-1 与内皮 EDHF 血管运动机制之间存在显著的相互作用,而在氧化应激存在下(Nrf2 小鼠)这种相互作用会减少。我们的研究结果间接表明,代谢振荡可能参与内皮介导的皮肤血管运动的机制,而在代谢紊乱存在的情况下,这种机制可能会发生改变。