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Changes in the rat urinary bladder after the relief of outflow obstruction – tracing targets for treatment of persistent symptoms in patients

Andersson, Karl Erik LU orcid and Uvelius, Bengt LU (2022) In Frontiers in Urology 2.
Abstract

Studies on patients with bladder outflow obstruction who have undergone surgery for benign prostatic hyperplasia, successfully relieving the obstruction, have revealed a persistence of storage symptoms associated with detrusor overactivity (DO) in 20% to 40% of patients. To study the underlying mechanisms, we have used a common rat model of obstruction/de-obstruction, assuming that non-voiding contractions can be used as a surrogate parameter for DO in humans. Using microarray analysis and electron microscopic images from obstructed and de-obstructed bladder tissue we have tried to identify changes that could serve as a basis for the search of new targets for drugs. Even if voiding function is rapidly normalized after release of outflow... (More)

Studies on patients with bladder outflow obstruction who have undergone surgery for benign prostatic hyperplasia, successfully relieving the obstruction, have revealed a persistence of storage symptoms associated with detrusor overactivity (DO) in 20% to 40% of patients. To study the underlying mechanisms, we have used a common rat model of obstruction/de-obstruction, assuming that non-voiding contractions can be used as a surrogate parameter for DO in humans. Using microarray analysis and electron microscopic images from obstructed and de-obstructed bladder tissue we have tried to identify changes that could serve as a basis for the search of new targets for drugs. Even if voiding function is rapidly normalized after release of outflow obstruction and many of the morphological changes are reversed, the microarray analysis revealed that the de-obstructed rat bladder has gene expressions, structural, and functional properties that make it distinctly different from both control and obstructed bladders. We suggest that whole bladder arrays can be used for identifying cellular mechanisms that could be targets for drugs meant for treatment of persistent DO and LUTS after de-obstruction. Based on available array information for some membrane receptors and morphologic structures with corresponding changes in bladder function, it seems worthwhile to re-assess the development potential for e.g., endothelin receptor antagonists, purinergic receptor antagonists and Rho-kinase inhibitors.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
bladder, bladder outflow obstruction, cystometry, electron microscopy, microarrays, rat model
in
Frontiers in Urology
volume
2
article number
1027086
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85183447523
ISSN
2673-9828
DOI
10.3389/fruro.2022.1027086
language
English
LU publication?
yes
id
0f1a7afa-ee6e-49b8-af51-97a8bc3b9484
date added to LUP
2024-02-13 14:19:49
date last changed
2024-02-13 14:19:49
@article{0f1a7afa-ee6e-49b8-af51-97a8bc3b9484,
  abstract     = {{<p>Studies on patients with bladder outflow obstruction who have undergone surgery for benign prostatic hyperplasia, successfully relieving the obstruction, have revealed a persistence of storage symptoms associated with detrusor overactivity (DO) in 20% to 40% of patients. To study the underlying mechanisms, we have used a common rat model of obstruction/de-obstruction, assuming that non-voiding contractions can be used as a surrogate parameter for DO in humans. Using microarray analysis and electron microscopic images from obstructed and de-obstructed bladder tissue we have tried to identify changes that could serve as a basis for the search of new targets for drugs. Even if voiding function is rapidly normalized after release of outflow obstruction and many of the morphological changes are reversed, the microarray analysis revealed that the de-obstructed rat bladder has gene expressions, structural, and functional properties that make it distinctly different from both control and obstructed bladders. We suggest that whole bladder arrays can be used for identifying cellular mechanisms that could be targets for drugs meant for treatment of persistent DO and LUTS after de-obstruction. Based on available array information for some membrane receptors and morphologic structures with corresponding changes in bladder function, it seems worthwhile to re-assess the development potential for e.g., endothelin receptor antagonists, purinergic receptor antagonists and Rho-kinase inhibitors.</p>}},
  author       = {{Andersson, Karl Erik and Uvelius, Bengt}},
  issn         = {{2673-9828}},
  keywords     = {{bladder; bladder outflow obstruction; cystometry; electron microscopy; microarrays; rat model}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Urology}},
  title        = {{Changes in the rat urinary bladder after the relief of outflow obstruction – tracing targets for treatment of persistent symptoms in patients}},
  url          = {{http://dx.doi.org/10.3389/fruro.2022.1027086}},
  doi          = {{10.3389/fruro.2022.1027086}},
  volume       = {{2}},
  year         = {{2022}},
}