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Sildenafil Ameliorates Cardiomyopathy in mdx Mice
Author(s) -
Parchen Candace M.,
Percival Justin M.,
Dai DaoFu,
Gray Heidi N,
Froehner Stanley C.,
Beavo Joseph A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.891.1
Subject(s) - sildenafil , duchenne muscular dystrophy , cgmp specific phosphodiesterase type 5 , dystrophin , mdx mouse , cardiomyopathy , medicine , muscular dystrophy , erectile dysfunction , endocrinology , cardiology , heart failure , pharmacology
Duchenne muscular dystrophy (DMD) is the most prevalent type of muscular dystrophy and is the result of an X‐linked mutation in the dystrophin gene. The progression of skeletal muscle damage is rapid in DMD patients and cardiomyopathy soon follows. We have investigated whether or not sildenafil citrate, a phosphodiesterase 5 (PDE5) inhibitor, can be used to ameliorate the age‐related cardiac dysfunction in dystrophin‐null (mdx) mice, a mouse model of DMD. Using echocardiography, we show that chronic sildenafil treatment improves several functional deficits in the cardiac performance of aged mdx mice. Collagen VI levels are also lower in the hearts of sildenafil‐treated mdx mice, suggesting a remodeling of the extracellular matrix. This is the first study to report a cardioprotective effect of PDE5 inhibition in aged mdx mice. Overall, the data suggest that PDE5 inhibitors could be a useful treatment for the cardiomyopathy suffered by DMD patients. This work was supported by NIH grants DK21723 (JAB), NS059514 (SCF), MDA Development Grant (JMP) and Charley's Fund (SCF and JAB).