Cocks Matthew, Wagenmakers Anton J M
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Tom Reilly Building, Byrom Street, Liverpool, L3 3AF, UK.
J Physiol. 2016 Apr 15;594(8):2245-57. doi: 10.1113/JP270329. Epub 2015 Apr 16.
It is becoming increasingly apparent that a high vasodilator response of the skeletal muscle microvasculature to insulin and exercise is of critical importance for adequate muscle perfusion and long-term microvascular and muscle metabolic health. Previous research has shown that a sedentary lifestyle, obesity and ageing lead to impairments in the vasodilator response, while a physically active lifestyle keeps both microvascular density and vasodilator response high. To investigate the molecular mechanisms behind these impairments and the benefits of exercise training interventions, our laboratory has recently developed quantitative immunofluorescence microscopy methods to measure protein content of eNOS and NAD(P)Hoxidase specifically in the endothelial layer of capillaries and arterioles of human skeletal muscle. As eNOS produces nitric oxide (NO) and NAD(P)Hoxidase produces superoxide anions (O2 (-) , quenching NO) we propose that the eNOS/NAD(P)Hoxidase protein ratio is a marker of vasodilator capacity. The novel methods show that endurance training (ET) and high intensity interval training (HIT), generally regarded as a time-efficient alternative to ET, increase eNOS protein content and the eNOS/NADP(H)oxidase protein ratio in previously sedentary lean and obese young men. Resistance exercise training had smaller but qualitatively similar effects. Western blot data of other laboratories suggest that endurance exercise training leads to similar changes in sedentary elderly men. Future research will be required to investigate the relative importance of other sources and tissues in the balance between NO and O2 (-) production seen by the vascular smooth muscle layer of terminal arterioles.
越来越明显的是,骨骼肌微血管对胰岛素和运动的高血管舒张反应对于充足的肌肉灌注以及长期的微血管和肌肉代谢健康至关重要。先前的研究表明,久坐不动的生活方式、肥胖和衰老会导致血管舒张反应受损,而积极运动的生活方式可使微血管密度和血管舒张反应维持在较高水平。为了探究这些损伤背后的分子机制以及运动训练干预的益处,我们实验室最近开发了定量免疫荧光显微镜方法,以特异性测量人骨骼肌毛细血管和小动脉内皮层中eNOS和NAD(P)H氧化酶的蛋白质含量。由于eNOS产生一氧化氮(NO),而NAD(P)H氧化酶产生超氧阴离子(O2 (-),可淬灭NO),我们认为eNOS/NAD(P)H氧化酶蛋白比率是血管舒张能力的一个标志物。这些新方法表明,耐力训练(ET)和高强度间歇训练(HIT,通常被认为是一种省时的ET替代方法)可增加久坐不动的瘦人和肥胖青年男性的eNOS蛋白含量以及eNOS/NADP(H)氧化酶蛋白比率。抗阻运动训练的效果较小,但性质相似。其他实验室的蛋白质印迹数据表明,耐力运动训练会使久坐不动的老年男性产生类似的变化。未来的研究将需要调查在终末小动脉血管平滑肌层所观察到的NO和O2 (-)产生平衡中其他来源和组织的相对重要性。