Evaluation of the Therapeutic Utility of Phosphodiesterase 5A Inhibition in the MDX Mouse Model of Duchenne Muscular Dystrophy

摘要: Duchenne muscular dystrophy (DMD) is a devastating and ultimately fatal disease characterized by progressive muscle wasting weakness. DMD caused the absence of functional dystrophin protein, which in turn leads to reduced expression mislocalization dystrophin-associated proteins including neuronal nitric oxide (NO) synthase mu (nNOSμ). Disruption nNOSμ signaling results fatigue unopposed sympathetic vasoconstriction during exercise, thereby increasing contraction-induced damage dystrophin-deficient muscles. The loss normal exercise central vascular dysfunction proposed over 40 years ago be an important pathogenic mechanism DMD. Recent preclinical studies focused on circumventing defective dystrophic skeletal cardiac inhibiting phosphodiesterase 5A (PDE5A) have shown promising results. This review addresses nNOS muscles potential PDE5A inhibition as therapeutic approach for treatment cardiovascular deficits