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

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 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.

• Authors: Eva Degerman, René In 't Zandt, Annki Pålbrink, Måns Magnusson
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 139 Issue 8 Pg. 685-691 (Aug 2019) ISSN: 1651-2251 [Electronic] England
• PMID: 31145014 (Publication Type: Journal Article)

Chemical References

• Mineralocorticoid Receptor Antagonists
• Quinolones
• Vasopressins
• Spironolactone
• cilostamide
• Rolipram

Topics

• Animals
• Disease Models, Animal
• Endolymphatic Hydrops (chemically induced, diagnostic imaging, prevention & control)
• Female
• Magnetic Resonance Imaging
• Mice
• Mice, Inbred CBA
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Quinolones
• Rolipram
• Spironolactone (therapeutic use)
• Vasopressins