Dehydration effects of a V2 antagonist on endolymphatic hydrops in guinea pigs

Hear Res. 2016 Feb;332:151-159. doi: 10.1016/j.heares.2015.12.017. Epub 2015 Dec 21.


We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH.

Keywords: Endolymphatic hydrops; Meniere's disease; OPC-41061; V2 receptor antagonist; Vasopressin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Administration, Topical
  • Animals
  • Antidiuretic Hormone Receptor Antagonists / administration & dosage
  • Antidiuretic Hormone Receptor Antagonists / pharmacology*
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology*
  • Disease Models, Animal
  • Endolymphatic Hydrops / blood
  • Endolymphatic Hydrops / drug therapy*
  • Endolymphatic Hydrops / physiopathology
  • Endolymphatic Sac / drug effects*
  • Endolymphatic Sac / metabolism
  • Endolymphatic Sac / physiopathology
  • Female
  • Guinea Pigs
  • Meniere Disease / blood
  • Meniere Disease / drug therapy
  • Meniere Disease / physiopathology
  • Osmolar Concentration
  • Receptors, Vasopressin / drug effects*
  • Receptors, Vasopressin / metabolism
  • Tolvaptan
  • Vasopressins / blood
  • Water-Electrolyte Balance / drug effects*


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Receptors, Vasopressin
  • Vasopressins
  • Tolvaptan