Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle
Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle
复制标题
DOI：
10.1152/ajpheart.00534.2011
复制
发表时间：
2012-03-01
影响因子：
4.8
通讯作者：
Tsutsui, Hiroyuki
中科院分区：
文献类型：
--
作者：
Inoue, Naoki;Kinugawa, Shintaro;Tsutsui, Hiroyuki
井上N，木川S，Suga T，Yokota T，Hirabayashi K，黑田S，Okita K，Tsutsui H。血管紧张素II诱导的运动能力降低与骨骼肌氧化应激增加有关。Am J Physiol心圈Physiol 302：H1202-H1210,2012。首次发表于2011年12月30日；doi：10.1152/ajpheart.00534.2011。-已知血管紧张素II(AngII)诱导的氧化应激参与心血管疾病的发病。我们已经报道，骨骼肌中的氧化应激可以限制小鼠的运动能力(16)。因此，我们假设Ang II可能通过增强氧化应激来损害骨骼肌能量代谢，限制运动能力。将Ang II(50 ng·kg~(-1)·min~(-1))或赋形剂通过皮下埋植渗透压微泵注入雄性C57BL/6J小鼠体内，连续7天。血管紧张素转换酶II不改变体重、骨骼肌重、血压、心脏结构或功能。对小鼠进行跑步机测试，并对呼出的气体进行分析。与车辆相比，Ang II的力竭功(垂直距离x体重)和最大摄氧量显著减少。在分离的骨骼肌线粒体中，Ang II和Vehicle的ADP依赖性呼吸相似，但Ang II的ADP非依赖性呼吸显著增加。此外，Ang II的复合体I和III的活性降低。Ang II小鼠骨骼肌的NAD(P)H氧化酶活性和荧光素化学发光的超氧化物歧化产物显著增加。用NAD(P)H氧化酶活性抑制剂载脂蛋白(Apoynin)(饮用水中10 mmoL/L)处理Ang II小鼠，可完全抑制NAD(P)H氧化酶活性，提高运动能力、线粒体呼吸和骨骼肌复合活动。血管紧张素Ⅱ诱导的氧化应激可损害骨骼肌线粒体呼吸，限制运动能力。
Inoue N, Kinugawa S, Suga T, Yokota T, Hirabayashi K, Kuroda S, Okita K, Tsutsui H. Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle. Am J Physiol Heart Circ Physiol 302: H1202-H1210, 2012. First published December 30, 2011; doi:10.1152/ajpheart.00534.2011.-Angiotensin II (ANG II)-induced oxidative stress has been known to be involved in the pathogenesis of cardiovascular diseases. We have reported that the oxidative stress in skeletal muscle can limit exercise capacity in mice (16). We thus hypothesized that ANG II could impair the skeletal muscle energy metabolism and limit exercise capacity via enhancing oxidative stress. ANG II (50 ng.kg(-1).min(-1)) or vehicle was infused into male C57BL/6J mice for 7 days via subcutaneously implanted osmotic minipumps. ANG II did not alter body weight, skeletal muscle weight, blood pressure, cardiac structure, or function. Mice were treadmill tested, and expired gases were analyzed. The work to exhaustion (vertical distance x body weight) and peak oxygen uptake were significantly decreased in ANG II compared with vehicle. In mitochondria isolated from skeletal muscle, ADP-dependent respiration was comparable between ANG II and vehicle, but ADP-independent respiration was significantly increased in ANG II. Furthermore, complex I and III activities were decreased in ANG II. NAD(P)H oxidase activity and superoxide production by lucigenin chemiluminescence were significantly increased in skeletal muscle from ANG II mice. Treatment of ANG II mice with apocynin (10 mmol/l in drinking water), an inhibitor of NAD(P)H oxidase activation, completely inhibited NAD(P)H oxidase activity and improved exercise capacity, mitochondrial respiration, and complex activities in skeletal muscle. ANG II-induced oxidative stress can impair mitochondrial respiration in skeletal muscle and limit exercise capacity.