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Thus, we hypothesize that ischemic postconditioning (IPostC) protects hearts against ischemic\/reperfusion (I\/R) injury through an nNOS-mediated pathway. Isolated mouse hearts were subjected to I\/R injury in a Langendorff apparatus, H9C2 cells and primary neonatal rat cardiomyocytes were subjected to hypoxia\/reoxygenation (H\/R) <jats:italic>in vitro<\/jats:italic>. IPostC, compared with I\/R, decreased infarct size and improved cardiac function, and the selective nNOS inhibitors abolished these effects. IPostC recovered nNOS activity and arginase expression. IPostC also increased AMP kinase (AMPK) phosphorylation and alleviated oxidative stress, and nNOS and AMPK inhibition abolished these effects. IPostC increased nitrotyrosine production in the cytosol but decreased it in mitochondria. Enhanced phospholamban (PLB) phosphorylation, normalized SR function and decreased Ca<jats:sup>2+<\/jats:sup> overload were observed following the recovery of nNOS activity, and nNOS inhibition abolished these effects. Similar effects of IPostC were demonstrated in cardiomyocytes <jats:italic>in vitro<\/jats:italic>. IPostC decreased oxidative stress partially by regulating uncoupled nNOS and the nNOS\/AMPK\/peroxisome proliferator-activated receptor gamma coactivator 1 alpha\/superoxide dismutase axis, and improved SR function through increasing SR Ca<jats:sup>2+<\/jats:sup> load. These results suggest that IPostC protected hearts against I\/R injury via an nNOS-mediated pathway.<\/jats:p>","DOI":"10.1038\/cddis.2016.108","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T12:47:42Z","timestamp":1463057262000},"page":"e2222-e2222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Ischemic postconditioning protects the heart against ischemia\u2013reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria"],"prefix":"10.1038","volume":"7","author":[{"given":"L","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,12]]},"reference":[{"key":"BFcddis2016108_CR1","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1161\/CIRCULATIONAHA.111.041814","volume":"125","author":"X Ma","year":"2012","unstructured":"Ma X, Liu H, Foyil SR, Godar RJ, Weinheimer CJ, Hill JA et al. 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