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Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF\u20101\u2014key humoral mediator of exercise training\u2014inhibits myocardial NHE\u20101, at least in normotensive rats. Therefore, we hypothesize that IGF\u20101 by hampering NHE\u20101 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NHE\u20101 activity [proton efflux (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/apha13092-math-0001.png\" xlink:title=\"urn:x-wiley:17481708:media:apha13092:apha13092-math-0001\"\/>) mmol\u00a0L<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>], expression and phosphorylation; H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence\/absence of IGF\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IGF\u20101 significantly decreased NHE\u20101 activity (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/apha13092-math-0002.png\" xlink:title=\"urn:x-wiley:17481708:media:apha13092:apha13092-math-0002\"\/> at pH<jats:sub>i<\/jats:sub> 6.95: 1.39\u00a0\u00b1\u00a00.32, n\u00a0=\u00a09 vs C 3.27\u00a0\u00b1\u00a00.3, n\u00a0=\u00a020, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05); effect prevented by AG1024, an antagonist of IGF\u20101 receptor (2.7\u00a0\u00b1\u00a00.4, n\u00a0=\u00a07); by the PI3K inhibitor wortmannin (3.14\u00a0\u00b1\u00a00.41, n\u00a0=\u00a07); and the AKT inhibitor MK2206 (3.37\u00a0\u00b1\u00a00.43, n\u00a0=\u00a014). Moreover, IGF\u20101 exerted an antioxidant effect revealed by a significant reduction in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production accompanied by an increase in SOD activity. In addition, IGF\u20101 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IGF\u20101 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE\u20101 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13092","type":"journal-article","created":{"date-parts":[[2018,5,13]],"date-time":"2018-05-13T09:20:39Z","timestamp":1526203239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Cardioprotective role of IGF\u20101 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE\u20101 activity"],"prefix":"10.1111","volume":"224","author":[{"given":"A. 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