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Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle
| Title: | Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle |
| Authors: | Inoue, Naoki Browse this author | | Kinugawa, Shintaro Browse this author →KAKEN DB | | Suga, Tadashi Browse this author | | Yokota, Takashi Browse this author →KAKEN DB | | Hirabayashi, Kagami Browse this author | | Kuroda, Satoshi Browse this author →KAKEN DB | | Okita, Koichi Browse this author →KAKEN DB | | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | mitochondria | | reduced nicotinamide adenine dinucleotide phosphatase oxidase | | oxygen uptake |
| Issue Date: | 2012 |
| Publisher: | American Physiological Society |
| Journal Title: | American Journal of Physiology-Heart and Circulatory Physiology |
| Volume: | 302 |
| Issue: | 5 |
| Start Page: | H1202 |
| End Page: | H1210 |
| Publisher DOI: | 10.1152/ajpheart.00534.2011 |
| Abstract: | 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 × 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/76767 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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