Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy

• DOI: 10.1073/pnas.250379497
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Mikael Sander; Bahman Chavoshan; Shannon A. Harris; Susan T. Iannaccone; James T. Stull; Gail D. Thomas; Ronald G. Victor
• Keywords: Sarcolemma; ITGA7

Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutation of the gene encoding cytoskeletal protein dystrophin. Despite wealth recent information about molecular basis DMD, effective treatment for this does not exist because mechanism which dystrophin deficiency produces clinical phenotype unknown. In both mouse and human skeletal muscle, results in loss neuronal nitric oxide synthase, normally localized to sarcolemma as part dystrophin–glycoprotein complex. Recent studies mice suggest that muscle-derived may play key role regulation blood flow within exercising muscle blunting vasoconstrictor response α-adrenergic receptor activation. Here we report protective defective children with (measured decrease oxygenation) reflex sympathetic activation was blunted during exercise dystrophic muscles. contrast, intact healthy those polymyositis or limb-girdle dystrophy, diseases do result synthase. This investigation suggests unopposed vasoconstriction constitute heretofore unappreciated vascular contributing pathogenesis DMD.