Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp6889-list-0001">Dystrophin deficiency disrupts sarcolemmal targeting of neuronal nitric oxide synathase, resulting in functional muscle ischaemia.Chronic treatment of dystrophic mice with an inorganic nitric oxide (NO) donor alleviates this ischaemia and improves many features of the dystrophic phenotype.The present study translates this preclinical work by showing that a single oral dose of sodium nitrate,which serves as a NO donor when reduced to circulating nitrite by the commensal bacteria in the oral cavity, alleviates functional muscle ischaemia and restores normal blood flow regulation in human patients with dystrophinopathy.The results of the present study further support the mechanistic hypothesis that circulating nitrite serves as an alternative NO donor when reduced by deoxyhaemoglobin and/or deoxymyoglobin in exercising muscle.