Andrea Mietens

Caroline Feuerstacke

Dieter Müller

Friedrich Grimminger

Gerrit Eichner

M Mewe

Ralf Middendorff

Ralph Theo Schermuly

Sabine Tasch

BMC Pharmacology

English

PubMed

Crossref

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

Ralph Schermuly

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Acute effects of phosphodiesterase 5 (PDE5)
inhibition, ANP and NO on epididymal
contractility are preserved despite chronic PDE5
exposure
Andrea Mietens1*, Caroline Feuerstacke1, Sabine Tasch1, Gerrit Eichner2, Ralph Theo Schermuly3,
Friedrich Grimminger3, Dieter Müller1, Ralf Middendorff1
From 5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications
Halle, Germany. 24-26 June 2011
Background
To acquire motility and their fertilizing capacity, immo-
tile 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. Phos-
phodiesterases (PDEs) hydrolyzing cGMP control intra-
cellular 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 pos-
sible 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 loca-
lized PDE5 within the epididymal duct to smooth mus-
cle 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 fre-
quency 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-orche-
strated process of epididymal duct contractility and sug-
gest, however, that in the epididymis side effects of
therapeutically used sildenafil seem to be unlikely.
Acknowledgements
This work was supported by grants from the Deutsche
Forschungsgemeinschaft KFO 181/1.* Correspondence: andrea.mietens@anatomie.med.uni-giessen.de
1Department of Anatomy and Cell Biology, Justus Liebig University, Giessen,
Germany
Full list of author information is available at the end of the article
Mietens et al. BMC Pharmacology 2011, 11(Suppl 1):P47
http://www.biomedcentral.com/1471-2210/11/S1/P47
© 2011 Mietens et al; licensee 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.
Author details
1Department of Anatomy and Cell Biology, Justus Liebig University, Giessen,
Germany. 2Mathematical Institute, Justus Liebig University, Giessen, Germany.
3Department of Internal Medicine, Justus Liebig University, Giessen,
Germany.
Published: 1 August 2011
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.
2. Mewe M, Bauer CK, Schwarz JR, Middendorff R: Mechanisms regulating
spontaneous contractions in the bovine epididymal duct. Biol Reprod
2006, 75:651-651.
doi:10.1186/1471-2210-11-S1-P47
Cite this article as: Mietens et al.: Acute effects of phosphodiesterase 5
(PDE5) inhibition, ANP and NO on epididymal contractility are
preserved despite chronic PDE5 exposure. BMC Pharmacology 2011 11
(Suppl 1):P47.
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Page 2 of 2


Mechanisms regulating spontaneous contractions in the bovine epididymal duct. Biol Reprod

Regulation of spontaneous contractile activity in the bovine epididymal duct by cyclic guanosine 5’-monophosphate- dependent pathways. Endocrinology

Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3363242

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

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