The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.
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.
Takeda
Taizo
T
Department of Otolaryngology, Kochi Medical School, Kohasu, Oko-cho Nankoku, Kochi 783-8505, Japan. takedat@kochi-ms.ac.jp
Sawada
Shoichi
S
Takeda
Setsuko
S
Kitano
Hiroya
H
Suzuki
Mikio
M
Kakigi
Akinobu
A
Takeuchi
Shunji
S
D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D018159:Endolymphatic Hydrops / Q000139:chemically induced / Q000188:drug therapy*; D004712:Endolymphatic Sac / Q000098:blood supply / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009997:Osmotic Pressure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014667:Vasopressins / Q000009:adverse effects
D065092:Antidiuretic Hormone Receptor Antagonists; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D001552:Benzazepines; D012333:RNA, Messenger; D014667:Vasopressins; C076251:mozavaptan