Volume 11 Supplement 1

5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

Acute effects of phosphodiesterase 5 (PDE5) inhibition, ANP and NO on epididymal contractility are preserved despite chronic PDE5 exposure

  • Andrea Mietens1Email author,
  • Caroline Feuerstacke1,
  • Sabine Tasch1,
  • Gerrit Eichner2,
  • Ralph Theo Schermuly3,
  • Friedrich Grimminger3,
  • Dieter Müller1 and
  • Ralf Middendorff1
BMC Pharmacology201111(Suppl 1):P47

https://doi.org/10.1186/1471-2210-11-S1-P47

Published: 1 August 2011

Background

To acquire motility and their fertilizing capacity, immotile spermatozoa have to transit from the testis through the epididymal duct to the distal parts of the organ where spermatozoa are stored until ejaculation. This transit mainly relies on contractions of the epididymal peritubular smooth muscle layer and various factors, including cGMP, contribute to its fine regulation [1, 2]. Atrial natriuretic peptide (ANP) and nitric oxide (NO) affect contractility via cGMP-dependent pathways. Phosphodiesterases (PDEs) hydrolyzing cGMP control intracellular cGMP levels and thus limit a given cGMP signal. Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. Besides its use for the treatment of erectile dysfunction, sildenafil has gained importance as a therapeutic agent against pulmonary hypertension. Thus, an increasing number of young patients is exposed to chronic PDE5 inhibition. Currently, there is still very little knowledge about the occurrence and functional importance of PDEs in the epididymis and more specifically about possible effects or side effects of sildenafil on epididymal function.

Materials and methods

RT-PCR combined with laser-assisted microdissection, Western blotting and organ bath studies were used to investigate occurrence and functional aspects of PDE5 in epidiymal tissue from man and rat.

Results

Western blotting showed PDE5 expression in human epididymis. Immunohistochemistry together with RT-PCR analyses after laser capture microdissection localized PDE5 within the epididymal duct to smooth muscle cells, but not to epithelial cells. In organ bath studies with epididymal duct segments the cGMP-elevating agents ANP and NO resulted in a significant decrease of the frequency of spontaneous contractions. Sildenafil also significantly decreased spontaneous contractile frequency and its effect was additive to ANP and NO. However, after long-term exposure to sildenafil in vivo, spontaneous contractility of the epididymal duct was conserved as was the acute relaxing response towards ANP, NO and sildenafil. Expression of PDE5 remained unchanged.

Conclusion

Data demonstrate that PDE5 is an important member of cGMP signalling pathways regulating the finely-orchestrated process of epididymal duct contractility and suggest, however, that in the epididymis side effects of therapeutically used sildenafil seem to be unlikely.

Declarations

Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft KFO 181/1.

Authors’ Affiliations

(1)
Department of Anatomy and Cell Biology, Justus Liebig University
(2)
Mathematical Institute, Justus Liebig University
(3)
Department of Internal Medicine, Justus Liebig University

References

  1. Mewe M, Bauer CK, Müller D, Middendorff R: Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5'-monophosphate- dependent pathways. Endocrinology. 2006, 147: 2051-2062.View ArticlePubMedGoogle Scholar
  2. Mewe M, Bauer CK, Schwarz JR, Middendorff R: Mechanisms regulating spontaneous contractions in the bovine epididymal duct. Biol Reprod. 2006, 75: 651-651. 10.1095/biolreprod.106.054577.View ArticlePubMedGoogle Scholar

Copyright

© Mietens et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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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