Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice
Alessandra Medeiros, Natale P. L. Rolim, Rodrigo S. F. Oliveira, Kaleizu T. Rosa, Katt C. Mattos, Dulce E. Casarini, Maria Claúdia Irigoyen, Eduardo M. Krieger, José Eduardo Krieger, Carlos Eduardo Negrão, Patricia C. Brum
Journal of applied physiology
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
... 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.