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In this study, we examined the effects of compensating for lack of nNOS\u03bc with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice ( mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days\/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T<jats:sub>2<\/jats:sub>) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and <jats:sup>31<\/jats:sup>phosphorus MRS (<jats:sup>31<\/jats:sup>P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T<jats:sub>2<\/jats:sub> was attenuated ( P &lt; 0.05) in treated mdx and wild-type mice compared with untreated mdx. During training, resting T<jats:sub>2<\/jats:sub> values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater ( P &lt; 0.05) in treated mdx (&gt;90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater ( P &lt; 0.05) in treated mdx that trained than untreated mdx, with no differences in muscle oxidative capacity, as measured by <jats:sup>31<\/jats:sup>P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOS\u03bc. <\/jats:p>","DOI":"10.1152\/japplphysiol.00664.2018","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T16:03:10Z","timestamp":1554393790000},"page":"1737-1745","source":"Crossref","is-referenced-by-count":17,"title":["Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training"],"prefix":"10.1152","volume":"126","author":[{"given":"Abhinandan","family":"Batra","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravneet S.","family":"Vohra","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Florida, Gainesville, 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