The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops

Hear Res. 2003 Aug;182(1-2):9-18. doi: 10.1016/s0378-5955(03)00135-7.

Abstract

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

MeSH terms

  • Analysis of Variance
  • Animals
  • Antidiuretic Hormone Receptor Antagonists*
  • Aquaporin 2
  • Aquaporins / genetics
  • Aquaporins / metabolism*
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Endolymphatic Hydrops / chemically induced
  • Endolymphatic Hydrops / drug therapy*
  • Endolymphatic Sac / blood supply
  • Endolymphatic Sac / drug effects*
  • Gene Expression Regulation / drug effects
  • Guinea Pigs
  • Male
  • Osmotic Pressure
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vasopressins / adverse effects

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Aqp2 protein, rat
  • Aquaporin 2
  • Aquaporins
  • Benzazepines
  • RNA, Messenger
  • Vasopressins
  • mozavaptan