Effect of Exercise Training and Carvedilol Treatment on Cardiac Function and Structure in Sympathetic Hyperactivity‐Induced Heart Failure Mice

Abstract

The present investigation was undertaken to study the isolated effect of β‐blockers and exercise training (ET) on cardiac structure and function, and overall functional capacity in a genetic model of sympathetic hyperactivity induced heart failure in mice (DKO). DKO and wild type (WT) were studied from 3 to 5 mo of age, and randomly assigned into control, carvedilol‐treated and exercise‐trained groups. Eight weeks of carvedilol treatment or ET (sessions of 60 min, 5 days/wk) were performed. At 3 mo of age, no significant difference in FS or exercise capacity was observed between WT and DKO mice. At 5 mo of age, DKO presented exercise intolerance and higher HR associated with reduced FS. In addition, cardiac myocyte hypertrophy, ventricular fibrosis and capillary rarefaction were observed. ET and carvedilol similarly improved FS of DKO mice. The effect of ET was mainly associated with an improved exercise tolerance and improved skeletal muscle capillary density while β‐blocker therapy had a greater impact on cardiac reverse remodeling. Collectively, these data provide direct evidence for the beneficial effects of ET and carvedilol in DKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of ET and carvedilol empowers future studies associating both therapies.