{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:43:51Z","timestamp":1792421031817,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>New findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Does angiotensin\u00a0II directly induce skeletal muscle abnormalities?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Angiotensin\u00a0II induces skeletal muscle abnormalities and reduced exercise capacity. Mitochondrial dysfunction and a decreased number of oxidative fibres are manifest early, while muscle atrophy is seen later. Thus, angiotensin\u00a0II may play an important role in the skeletal muscle abnormalities observed in a wide variety of diseases.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Skeletal muscle abnormalities, such as mitochondrial dysfunction, a decreased percentage of oxidative fibres and atrophy, are the main cause of reduced exercise capacity observed in ageing and various diseases, including heart failure. The renin\u2013angiotensin system, particularly angiotensin\u00a0II (Ang\u00a0II), is activated in the skeletal muscle in these conditions. Here, we examined whether Ang\u00a0II could directly induce these skeletal muscle abnormalities and investigated their time course. Angiotensin\u00a0II (1000\u00a0ng\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>) or vehicle was administered to male C57BL\/6J mice (10\u201312\u00a0weeks of age) via subcutaneously implanted osmotic minipumps for 1 or 4\u00a0weeks. Angiotensin\u00a0II significantly decreased body and hindlimb skeletal muscle weights compared with vehicle at 4\u00a0weeks. In parallel, muscle cross\u2010sectional area was also decreased in the skeletal muscle at 4\u00a0weeks. Muscle RING finger\u20101 and atrogin\u20101 were significantly increased in the skeletal muscle from mice treated with Ang\u00a0II. In addition, cleaved caspase\u20103 and terminal deoxynucleotidyl trasferase\u2010mediated dUTP nick\u2010positive nuclei were significantly increased in mice treated with Ang\u00a0II at 1 and 4\u00a0weeks, respectively. Mitochondrial oxidative enzymes, such as citrate synthase, complex\u00a0I and complex\u00a0III activities were significantly decreased in the skeletal muscle from mice treated Ang\u00a0II at 1 and 4\u00a0weeks. NAD(P)H oxidase\u2010derived superoxide production was increased. NADH staining revealed that type\u00a0I fibres were decreased and type\u00a0IIb fibres increased in mice treated with Ang\u00a0II at 1\u00a0week. The work and running distance evaluated by a treadmill test were significantly decreased in mice treated with Ang\u00a0II at 4\u00a0weeks. Thus, Ang\u00a0II could directly induce the abnormalities in skeletal muscle function and structure.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2014.084095","type":"journal-article","created":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T06:40:10Z","timestamp":1420872010000},"page":"312-322","source":"Crossref","is-referenced-by-count":78,"title":["Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle"],"prefix":"10.1113","volume":"100","author":[{"given":"Tomoyasu","family":"Kadoguchi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Hokkaido University Graduate School of Medicine  Kita\u2010ku, Hokkaido Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Kinugawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Hokkaido University Graduate School of Medicine  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