Résumé
BackgroundDuchenne muscular dystrophy (DMD) is the most common genetic disease in children worldwide caused by the absence of dystrophin, characterized by progressive muscle degeneration and weakness. With increasing age, DMD patients also develop a progressive dilated cardiomyopathy (DCM). Despite knowing the cause of DMD, there are currently no treatments which can reverse its inevitable progression. We have previously shown overload that diastolic [Ca] ([Ca]d) and [Na] ([Na]d) overload in cardiomyocytes of DM mice model (mdx) which is age dependent. WBPA is the passive sinusoidal motion of the supine body back and forth, which produces pulsatile shear stress and shown to increase expression and phosphorylation of endothelial-derived nitric oxide synthase (eNOS, p-eNOS) which are cardioprotective. We have previously shown that WBPA reduces [Ca]d and [Na]d in skeletal muscle of mdx. We hypothesized that WBPA performed in mdx mice with established DCM (9-months-old) may improve [Ca]d and [Na]d and cardiac functions.MethodsMale WT and mdx mice were randomly assigned to four groupsa) WT, untreated (n = 19); b) WT, treated with WBPA (n = 20); c) mdx, untreated (n = 15); d) mdx, treated with WBPA (n = 18). WBPA was performed in awake mice for 1 hr daily 5 days a week, for 12 weeks. [Ca]d and [Na]d were measured by ion-selective microelectrodes.ResultsWBPA reduced [Ca]d and [Na]d overloads, decreased oxidative stress, and intracellular calpain activity. In addition, WBPA diminished cardiac hypertrophy and improved left ventricular function compared to non-WBPA treated mdx mice.ConclusionsThis study is the first to directly test the ability of endogenously produce nitric oxide via WBPA to ameliorate established cardiomyopathy in mdx mice: