Brum PC. Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice. Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca 2ϩ handling abnormalities and ventricular dysfunction

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... n sympathetic hyperactivity-induced HF mice. A cohort of male wildtype (WT) and congenic ␣ 2A/␣2C-adrenoceptor knockout (␣2A/ ␣ 2CARKO) mice with C57BL6/J genetic background (3-5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided Mmode echocardiography. The protein expression of ryanodine receptor (RyR), phospho-Ser 2809 -RyR, sarcoplasmic reticulum Ca 2ϩ ATPase (SERCA2), Na ϩ /Ca 2ϩ exchanger (NCX), phospholamban (PLN), phospho-Ser 16 -PLN, and phospho-Thr 17 -PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and ␣ 2A/␣2CARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, ␣ 2A/␣2CARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, ␣ 2A/␣2CARKO mice displayed increased phospho-Ser 16 -PLN (76%) and phospho-Ser 2809 -RyR (49%). ET in ␣ 2A/␣2CARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser 16 -PLN (30%) while it restored the expression of phospho-Ser 2809 -RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca 2ϩ handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.