Battault Sylvain, Singh François, Gayrard Sandrine, Zoll Joffrey, Reboul Cyril, Meyer Grégory
Laboratoire de Pharm-Ecologie Cardiovasculaire (EA4278), Faculty of Sciences, Avignon University, Avignon, France.
E.A. 3072, Fédération de Médecine Translationnelle, Faculty of Medicine, University of Strasbourg, Strasbourg, France.
Hypertens Res. 2016 Feb;39(2):70-8. doi: 10.1038/hr.2015.114. Epub 2015 Nov 5.
Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation.
运动训练是一种公认的通过增加一氧化氮（NO）生物利用度来改善血管内皮功能的方法。然而，在高血压患者中，与低强度和中等强度运动训练不同，持续高强度运动对内皮功能的有益作用尚不清楚，其潜在机制也仍然未知。本研究的目的是探讨高强度运动对自发性高血压大鼠（SHR）血管功能的影响，特别是对NO途径的影响。对WKY大鼠、久坐不动的SHR大鼠以及在跑步机上进行中等强度（SHR-MOD）和高强度（SHR-HI）运动的SHR大鼠（每天1小时；每周5天，共6周，分别以其最大有氧速度的55%和80%进行运动）进行了这些效应的研究。通过测量主动脉环等长力来评估内皮功能以及特定NO对乙酰胆碱介导的舒张的贡献。通过蛋白质免疫印迹法评估内皮型一氧化氮合酶（eNOS）的表达和磷酸化（ser1177）。使用电子顺磁共振评估主动脉组织中总主动脉和eNOS依赖性活性氧（ROS）的产生。尽管SHR-HI大鼠的主动脉中eNOS水平升高，但eNOS磷酸化未改变，与中等强度运动不同，高强度运动对内皮依赖性血管舒张没有有益作用。这一结果与SHR-HI大鼠主动脉中eNOS依赖性ROS产生增加有关。值得注意的是，使用再偶联剂BH4或硫醇还原剂可减弱SHR-HI大鼠主动脉中eNOS依赖性ROS的产生。总之，高强度运动对SHR内皮功能缺乏积极作用主要是由氧化还原依赖性eNOS解偶联所解释的，导致从NO生成转向O2(-)生成。
