Voluntary Exercise Enhances Cardiac Growth in Response to Chronic β‐Adrenergic Receptor Stimulation

Abstract

Exercise has been demonstrated to protect the heart against the adverse effects of cardiovascular disease. Given the prevalence of cardiovascular disease (CVD), the role that exercise plays in protecting the heart prior to CVD is an important area of research given its clinical implications. Therefore, this study aims to examine how voluntary exercise can impact the progression of heart failure. To do this, a mouse model with nine‐week‐old female and male CB6F1 hybrid mice was used to test the impact of voluntary wheel running on heart failure resulting from chronic β‐adrenergic receptor stimulation. Mice either exercised for five weeks on a voluntary wheel (EX) or remained sedentary during the duration of the study (SED). After three weeks, both SED and EX mice were administered either vehicle (VEH) or isoproterenol (ISO, 30mg/kg/day) via an osmotic pump for two weeks. In the EX group, mice were further divided into two groups: one that continued exercising while receiving ISO (EX+ISOe) and one that became sedentary (EX+ISOs). At the end of the treatment, morphometric data was collected including heart weight‐to‐tibia length (HW/TL). Significant cardiac growth was observed in the both males and females in the mice that exercised for the entire five weeks (EX+VEH) as compared to their sedentary counterparts (SED+VEH). Additionally, male and female mice that were sedentary for 21 days and received ISO (SED+ISO) had increased heart size in comparison to the control group (SED+VEH). In male and female EX+ISOs mice, both sexes had similar cardiac growth to the SED+ISO group. Finally, cardiac growth in both EX+ISOe males and female was greater than any of the other groups of mice. Our results suggest that there is an additive effect of both exercise and ISO causing this significant increase in size. This data is in contrast to previous studies that demonstrated forced exercise reduced cardiac hypertrophy in response to chronic β‐adrenergic receptor stimulation. To better understand these differences in our study, we are currently performing quantitative PCR on left ventricular tissue to identify changes in a number of hypertrophic gene markers. These investigations will allow us to better understand the cardioprotective effects of exercise on the progression of heart failure.Support or Funding InformationMurdock Faculty Start‐up Funding (SL)