This article is part of the supplement: 4th International Conference of cGMP Generators, Effectors and Therapeutic Implications

Poster presentation

Sildenafil ameliorates cardiomyopathy in dystrophin-null (mdx) mice

Candace M Parchen^1*, Dao-Fu Dai², Justin M Percival³, Monte Willis⁴, Stanley C Froehner² and Joseph A Beavo¹

• * Corresponding author: Candace M Parchen candace3@u.washington.edu

Author Affiliations

¹ Department of Pharmacology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA

² Department of Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA

³ Department of Physiology & Biophysics, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA

⁴ Department of Pathology and Laboratory Medicine, University of North Carolina 103 Mason Farm Road, Chapel Hill, North Carolina 27599, USA

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BMC Pharmacology 2009, 9(Suppl 1):P53 doi:10.1186/1471-2210-9-S1-P53

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2210/9/S1/P53

Published:

11 August 2009

© 2009 Parchen et al; licensee BioMed Central Ltd.

Background

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.

Results

Using echocardiography, we show that chronic sildenafil treatment prevents several functional deficits in the cardiac performance of aged mdx mice. Sildenafil treatment also prevents cardiac fibrosis from developing. Not only does sildenafil prevent cardiac dysfunction, but it also reverses established cardiomyopathy when treatment starts in aged mdx mice. This is the first study to report a cardioprotective and reversal effect of PDE5 inhibition in aged mdx mice.

Conclusion

Overall, the data suggest that PDE5 inhibitors could be a useful treatment for the cardiomyopathy suffered by DMD patients.

Acknowledgements

This work was supported by NIH grants DK21723 (JAB), NS059514 (SCF), MDA Development Grant (JMP) and Charley's Fund (SCF and JAB).