Method/Mechanism | Dosage Range | Model | Effects | Other | Reference |
---|---|---|---|---|---|
nNOS restoration Breeding with transgenic nNOS overexpressors Transfection with nNOS | N/A | mdx mouse Dystrophin/utrophin knockout mouse mdx mouse | Skeletal muscle: reduces inflammation, macrophage and neutrophil infiltration, damage Cardiac muscle: reduces fibrosis, macrophage infiltration, improves impulse conduction Skeletal muscle: increases DPC expression, NO production, reduces damage and fatigue, prevents force production loss | ||
˪-arginine supplementation | 200–1000 mg/kg/day | DMD patients mdx mouse | Skeletal muscle: increases DPC expression, reduces damage, fibrotic and fatty tissue infiltration, inflammatory cell infiltration, oxidative stress, improves grip strength, contractile function and reduces fatigability | Administered in combination with metformin and prednisone | |
PDE inhibition Sildenafil Tadalafil | 0.7–80 mg/kg/day 30–300 mg/kg/day | DMD patients mdx mouse DMD patients mdx mouse | Skeletal muscle: reduces collagen and inflammatory cell infiltration, improves sarcolemmal integrity Cardiac muscle: reduces membrane permeability, induces cardiac remodelling, improves heart function Skeletal muscle: improves functional ischemia, reduces contraction-induced damage, fibrotic infiltration, histological variability, improves exercise performance, increases expression of ETC. genes | ||
NO donation | 21–80 mg/kg/day | mdx mouse | Skeletal muscle: increases vascularisation, blood flow, exercise performance and strength, decreases free Ca2+ concentration, damage, inflammation, fibrotic and collagenous infiltration Cardiac muscle: decreases damage, inflammation, fibrotic and collagenous infiltration, improves cardiac function and architecture | Administered in combination with NSAIDs | |
Expansion of nitrate-nitrite-NO pool | 85 mg/L | mdx mouse | Skeletal muscle: does not improve mitochondrial deficits, increases damage and peroxynitrite production | Only one study to date | [107] |