Exercise training restores cardiac dysfunction and altered sarcoplasmic calcium reuptake in a genetic model of cardiomyopathy

We tested the hypothesis that exercise training (ET) would restore cardiac dysfunction and intracellular calcium regulation (ICR) in mice lacking α2A/α2C adrenoceptors(DKO). We studied a cohort of DKO and their wild type (WT) controls from 3–5 mo of age. Exercise training (ET) consisted of 8‐wk swimming session. Exercise capacity was measured using a graded treadmill protocol. Heart rate (HR) was determined by tail cuff. Fractional shortening (FS) by echocardiography. Cardiac sympathetic tone (CST) was estimated by pharmacological blockade. The protein expression of cardiac SERCA2a, phospholamban (PLN), phospho‐Ser16‐PLN, Na+/Ca2+ exchanger (NCX), ryanodine receptor (RYR) and phospho‐RYR2 were analyzed using Western blotting technique. At 5 mo of age, DKO displayed exercise intolerance and higher HR associated with significantly increased CST. In addition, DKO presented lower FS than WT mice. The impaired FS in DKO was paralleled by a reduction of SERCA2a and NCX expression. Conversely, phospho‐RYR2 was increased in DKO when compared with WT mice. ET prevented exercise intolerance, and it restored baseline HR, FS and CST. The improved FS was associated with restored SERCA and phospho‐RYR2 expression levels. Indeed, ET increased SERCA/PLB ratio in 5 mo‐old DKO mice. Collectively we provide direct evidence for the beneficial effects of ET on cardiac function of DKO associated with improved ICR. Supported by FAPESP#02/04588‐8 and 04/00745‐7.