Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy

Abstract

The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO-mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype.

Cross Talk between Nitric Oxide and Calcium-Calmodulin Regulates Ganoderic Acid Biosynthesis in Ganoderma lucidum under Heat Stress

“…Cytosolic Ca 2ϩ increases NO release, and the generation of NO induces the release of Ca 2ϩ (Table S2). Ca 2ϩ activates muscle growth and regeneration; however, NO represses muscle growth and regener-ation (32). This finding illustrates the complexity of the signal-regulating network.…”

Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management

“…However, the effects of exercise on muscle degeneration in dystrophinopathies, although not fully understood, can include damage due to structural fragility of muscles, metabolic abnormalities, nitric oxide abnormalities contributing to ischaemia during exercise, and reduced exercise capacity. 7,86–89 Eccentric muscle activity or exercise and high-resistance exercise or strength training should be avoided. 7,90 Submaximal aerobic exercise or activity has been recommended, especially early in the course of the disease—avoiding overexertion and overwork, and allowing adequate rest.…”

Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

“…28,29 Neuronal NOS (nNOS) interacts with dystrophin-associated glycoprotein complex at the sarcolemma in skeletal myocytes, and this association is lost in dystrophin deficiency. 28 However, in cardiomyocytes isolated from the mdx mouse, nNOS does not colocalize with dystrophin 30,31 but instead colocalizes with the ryanodine receptor 2 (RyR2) at the sarcoplasmic reticulum. 32 Endothelial NOS localizes to the Golgi complex and the sarcolemma caveolae.…”