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Impaired nerve-mediated relaxation of penile tissue from caveolin-1 deficient mice.

Shakirova, Yulia LU ; Hedlund, Petter LU and Swärd, Karl LU (2009) In European Journal of Pharmacology 602. p.399-405
Abstract
Caveolin-1-deficient mice are characterised by a high vascular NO production. Because NO-dependent smooth muscle relaxation is considered to play an important role in penile erection, it was hypothesized that the erectile function would be affected by genetic ablation of caveolae. This study assessed penile erectile mechanisms in caveolin-1 knockout (KO) mice ex vivo. Immunofluorescence confirmed caveolin-1 expression primarily in the endothelium surrounding the sinusoids of the corpus cavernosum, but also in smooth muscle cells of the sinusoidal bundles. In KO mice, caveolin-1 was absent, and the expression of the caveola-associated protein PTRF-Cavin was reduced. Nitric oxide synthase (endothelial and neuronal) and caveolin-3 levels were... (More)
Caveolin-1-deficient mice are characterised by a high vascular NO production. Because NO-dependent smooth muscle relaxation is considered to play an important role in penile erection, it was hypothesized that the erectile function would be affected by genetic ablation of caveolae. This study assessed penile erectile mechanisms in caveolin-1 knockout (KO) mice ex vivo. Immunofluorescence confirmed caveolin-1 expression primarily in the endothelium surrounding the sinusoids of the corpus cavernosum, but also in smooth muscle cells of the sinusoidal bundles. In KO mice, caveolin-1 was absent, and the expression of the caveola-associated protein PTRF-Cavin was reduced. Nitric oxide synthase (endothelial and neuronal) and caveolin-3 levels were not affected, and staining of the neuronal marker PGP 9.5 did not disclose any apparent change in the density or pattern of innervation. Moreover, no apparent morphological differences were noted. Functionally, the force response following stimulation of alpha(1)-adrenergic receptors, and the sensitivity to the Rho-kinase inhibitor Y27632, were unaltered, whereas relaxation of alpha(1)-precontracted corpus cavernosum in response to electrical field stimulation and the muscarinic agonist carbachol were impaired. The nitric oxide donor sodium nitroprusside produced less relaxation in KO as compared to wild type corpus cavernosum. We conclude that nerve-mediated dilatation of the corpus cavernosum is impaired in the absence of caveolin-1, and that this is due in part to reduced sensitivity of the target tissue to NO. All in all our data support an important role of caveolin-1 in penile erection. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
602
pages
399 - 405
publisher
Elsevier
external identifiers
  • wos:000263016900033
  • pmid:19068211
  • scopus:58149175655
ISSN
1879-0712
DOI
10.1016/j.ejphar.2008.11.033
language
English
LU publication?
yes
id
d02d4022-ffbe-4699-903d-cae262a3b7bd (old id 1276283)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19068211?dopt=Abstract
date added to LUP
2009-01-09 11:21:10
date last changed
2017-10-22 04:52:38
@article{d02d4022-ffbe-4699-903d-cae262a3b7bd,
  abstract     = {Caveolin-1-deficient mice are characterised by a high vascular NO production. Because NO-dependent smooth muscle relaxation is considered to play an important role in penile erection, it was hypothesized that the erectile function would be affected by genetic ablation of caveolae. This study assessed penile erectile mechanisms in caveolin-1 knockout (KO) mice ex vivo. Immunofluorescence confirmed caveolin-1 expression primarily in the endothelium surrounding the sinusoids of the corpus cavernosum, but also in smooth muscle cells of the sinusoidal bundles. In KO mice, caveolin-1 was absent, and the expression of the caveola-associated protein PTRF-Cavin was reduced. Nitric oxide synthase (endothelial and neuronal) and caveolin-3 levels were not affected, and staining of the neuronal marker PGP 9.5 did not disclose any apparent change in the density or pattern of innervation. Moreover, no apparent morphological differences were noted. Functionally, the force response following stimulation of alpha(1)-adrenergic receptors, and the sensitivity to the Rho-kinase inhibitor Y27632, were unaltered, whereas relaxation of alpha(1)-precontracted corpus cavernosum in response to electrical field stimulation and the muscarinic agonist carbachol were impaired. The nitric oxide donor sodium nitroprusside produced less relaxation in KO as compared to wild type corpus cavernosum. We conclude that nerve-mediated dilatation of the corpus cavernosum is impaired in the absence of caveolin-1, and that this is due in part to reduced sensitivity of the target tissue to NO. All in all our data support an important role of caveolin-1 in penile erection.},
  author       = {Shakirova, Yulia and Hedlund, Petter and Swärd, Karl},
  issn         = {1879-0712},
  language     = {eng},
  pages        = {399--405},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Impaired nerve-mediated relaxation of penile tissue from caveolin-1 deficient mice.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2008.11.033},
  volume       = {602},
  year         = {2009},
}