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Volume 9 Supplement 1

4th International Conference of cGMP Generators, Effectors and Therapeutic Implications

Sildenafil ameliorates cardiomyopathy in dystrophin-null (mdx) mice

BMC Pharmacology volume 9, Article number: P53 (2009) Cite this article

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).

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Authors and Affiliations

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

    Candace M Parchen & Joseph A Beavo

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

    Dao-Fu Dai & Stanley C Froehner

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

    Justin M Percival

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

    Monte Willis

Authors
  1. Candace M Parchen
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  2. Dao-Fu Dai
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  3. Justin M Percival
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  4. Monte Willis
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  5. Stanley C Froehner
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  6. Joseph A Beavo
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Corresponding author

Correspondence to Candace M Parchen.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Parchen, C.M., Dai, DF., Percival, J.M. et al. Sildenafil ameliorates cardiomyopathy in dystrophin-null (mdx) mice. BMC Pharmacol 9 (Suppl 1), P53 (2009). https://doi.org/10.1186/1471-2210-9-S1-P53

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  • DOI: https://doi.org/10.1186/1471-2210-9-S1-P53

Keywords

  • Cardiomyopathy
  • Muscular Dystrophy
  • Phosphodiesterase
  • Duchenne Muscular Dystrophy
  • Cardiac Dysfunction

BMC Pharmacology

ISSN: 1471-2210