Bumetanide-induced enlargement of the rat intrastrial space and effects of a vasopressin type 2 antagonist.
OBJECTIVE
Water homeostasis is essential for the inner ear to maintain the function of hearing and equilibrium. Bumetanide inhibits Na(+)-K(+)-2Cl(-) co-transporter (NKCC), which is expressed in the basolateral membrane of stria vascularis marginal cell, and it causes the enlargement of intrastrial space. Aquaporin (AQP) 2 is expressed in the perilymph side of stria vascularis basal cell, and the vasopressin type 2 antagonist OPC-31260 produces downregulation of AQP2 mRNA levels in the inner ear. The aim of this study is to investigate the influence of OPC-31260 on experimentally induced enlargement of the intrastrial space caused by bumetanide.


METHODS
Wistar rats were divided into two groups, a BUM group and an OPC-BUM group. The BUM group was exposed to bumetanide, and the OPC-BUM group was exposed to bumetanide after being premedicated with OPC-31260. The specimens of the stria vascularis were observed using transmission electron microscopy and analyzed quantitatively and statistically.


RESULTS
Morphological changes of intrastrial space enlargement occurred in both the BUM and OPC-BUM groups. The ratio of the areas of the intrastrial space area to the stria vascularis were calculated, and the OPC-BUM group mean showed a minimal difference from the BUM-group mean. However, there is no statistical difference.


CONCLUSIONS
Premedication of rats with OPC-31260 tended to reduce bumetanide-induced enlargement of the intrastrial space. This may indicate that the effect of bumetanide on the stria vascularis is much stronger than that of OPC-31260.
Nishimura
Masahiko
M
Department of Otolaryngology, Osaka University Graduate School of Medicine, Osaka, Japan.
Kakigi
Akinobu
A
Takeda
Taizo
T
Okada
Teruhiko
T
Doi
Katsumi
K
D000284:Administration, Oral; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2 / Q000378:metabolism; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D002034:Bumetanide; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006706:Homeostasis / Q000187:drug effects; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D013316:Stria Vascularis / Q000187:drug effects* / Q000473:pathology*
D065092:Antidiuretic Hormone Receptor Antagonists; D051399:Aquaporin 2; D001552:Benzazepines; D002034:Bumetanide; C076251:mozavaptan