Duchenne muscular dystrophy (DMD) is an inherited crippling disease of childhood. Becker muscular dystrophy (BMD) is a milder form of the disease that often is diagnosed in early adulthood. Both dystrophies impair quality of life and shorten life expectancy. The gene defect common to both diseases was discovered 25 years ago. This discovery led to the development of disease models in mice, which has improved our knowledge of the disease process but has not yet led to major breakthroughs in the treatment of patients. We propose a new study in mice and in patients with DMD/BMD that aims to find effective treatment for muscular dystrophy. Our study is based on recent work showing that drugs that supply nitric oxide (NO) benefit muscular dystrophy by decreasing muscle injury and fatigue. However, the effects of these NO-donating drugs have not yet been tested in patients with muscular dystrophy. We also do not know exactly how the drugs decrease muscle injury. We now propose studies to determine if the drugs' major effect is to increase blood flow to the diseased muscles. We will begin by studying mice with muscular dystrophy to determine if short-term treatment (1-7 days) with an NO-donating drug called naproxcinod increases muscle blood flow and, as a result, increases the ability to exercise. We also will see if treatment with naproxcinod improves heart function. In the next phase of the research, we will treat mice for 6 months with naproxcinod to see if the beneficial effects on skeletal muscle and the heart are maintained and to make sure that there are no negative side effects of the drug. Finally, we will determine if naproxcinod also increases muscle blood flow in patients with muscular dystrophy. We will study 12 men with BMD and 12 boys with DMD. If the studies are positive and the drug increases muscle blood flow in patients with muscular dystrophy, this may allow them to perform more exercise with less risk of injury and less fatigue. Over time, this may slow progression of the disease and improve the quality of life. If naproxcinod also has a beneficial effect on the heart, this could reduce heart problems and allow patients to live longer. Naproxcinod has already been tested in patients with arthritis and high blood pressure and has been found to be very safe. However, it is still an experimental drug and is not yet used to treat any disease. Our hope is that at the end of our 3-year study, we will have enough convincing evidence of the benefits of naproxcinod to propose clinical trials in patients with muscular dystrophy that could begin shortly thereafter.