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Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone : a rationale for understanding the diversity of treatment responses in hydropic inner ear disease

Degerman, Eva LU orcid ; In 't Zandt, René LU orcid ; Pålbrink, Annki LU and Magnusson, Måns LU orcid (2019) In Acta Oto-Laryngologica 139(8). p.685-691
Abstract

Background: The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Aims/objectives: Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Material and methods: Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with... (More)

Background: The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Aims/objectives: Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Material and methods: Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with immunohistochemistry. Results: Spironolactone prevents EH induced by vasopressin and rolipram, but not hydrops induced by cilostamide. The aldosterone target ENaC and the mineralocorticoid receptor were expressed in the human saccule sensory epithelium. Conclusions: The effect of spironolactone on EH appears to be pathway-dependent and may provide explanations why certain drugs may be effective in some patients with hydropic ear disease while not in others. Significance: Extrapolating this finding to the clinic supports that a personalized medicine approach is probably necessary in the treatment of diseases involving EH, as different pathways may be needed to be targeted for treatment.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oto-Laryngologica
volume
139
issue
8
pages
7 pages
publisher
Taylor & Francis
external identifiers
  • pmid:31145014
  • scopus:85066619046
ISSN
1651-2251
DOI
10.1080/00016489.2019.1616819
language
English
LU publication?
yes
id
4e388ef5-aa39-4656-a972-b8094f73ef58
date added to LUP
2019-06-19 10:14:55
date last changed
2024-02-15 12:07:31
@article{4e388ef5-aa39-4656-a972-b8094f73ef58,
  abstract     = {{<p>Background: The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Aims/objectives: Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Material and methods: Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with immunohistochemistry. Results: Spironolactone prevents EH induced by vasopressin and rolipram, but not hydrops induced by cilostamide. The aldosterone target ENaC and the mineralocorticoid receptor were expressed in the human saccule sensory epithelium. Conclusions: The effect of spironolactone on EH appears to be pathway-dependent and may provide explanations why certain drugs may be effective in some patients with hydropic ear disease while not in others. Significance: Extrapolating this finding to the clinic supports that a personalized medicine approach is probably necessary in the treatment of diseases involving EH, as different pathways may be needed to be targeted for treatment.</p>}},
  author       = {{Degerman, Eva and In 't Zandt, René and Pålbrink, Annki and Magnusson, Måns}},
  issn         = {{1651-2251}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{685--691}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oto-Laryngologica}},
  title        = {{Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone : a rationale for understanding the diversity of treatment responses in hydropic inner ear disease}},
  url          = {{http://dx.doi.org/10.1080/00016489.2019.1616819}},
  doi          = {{10.1080/00016489.2019.1616819}},
  volume       = {{139}},
  year         = {{2019}},
}