Nitric oxide ameliorates muscular dystrophy

Abstract

IntroductionDuchenne muscular dystrophy (DMD) is a lethal, X‐linked disorder associated with dystrophin deficiency that results in chronic inflammation, sarcolemma damage, and severe skeletal muscle degeneration. Effective drug therapy for reducing or delaying the skeletal muscle weakness and necrosis could be a great hope for individuals suffering from DMD. Here we hypothesized that the early treatment of mdx neonatal mice with L‐arginine could ameliorate muscular dystrophy.MethodsSeven days old animals were treated IP daily with 800 mg/kg of L‐arginine (L‐arg) or saline (control group) for six weeks. The hind limb skeletal muscle, the Tibialis Anterior (TA) was investigated. The following parameters were evaluated: the force generated, muscle resistance to mechanical stress, the level of centronucleation, detection of utrophine by immonostaining and western blot, creatine kinase (CK) activity and, nitric oxide (NO) production.ResultsOur results show that: 1) TA weight and the percentage of centronucleation in L‐arg treated animals were significantly lower than in control animals despite the fact that body weights were not different; 2) L‐arg improved TA ability to resist injury caused by high‐stress contractions; 3) CK level was two time higher in control animals compared to L‐arg treated mice, however, this difference was not statistically significant; 4) NO production was significantly higher in L‐arg treated animals; 5) there was no evidence that the improvements observed in L‐arg treated mice were associated with utrophin upregulation.ConclusionOur data strengthen the usefulness of L‐Arginine as a powerful pharmacological tool in Duchenne muscular dystrophies. However, the improvements observed were not associated with utrophin upregulation.Support or Funding InformationMuscular Dystrophy Association (MDA)Canadian Institutes of Health Research (CIHR)