title: Bumetanide-induced enlargement of the intercellular space in the stria vascularis requires an active Na+-K+-ATPase.
abstract: OBJECTIVE
  Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space of the stria vascularis, with an associated decline in the endocochlear DC potential (EP). The aim of this study was to determine the role played by the Na+-K+-ATPase in the bumetanide-induced enlargement of the intrastrial space, and to examine the importance of the balance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase to the physiological function of the stria vascularis.
  
  
  METHODS
  Albino guinea pigs were used in experiments involving perilymphatic perfusion, EP measurement and electron microscopy. The effects of bumetanide on the stria vascularis were examined following inhibition of the Na+-K+-ATPase by ouabain. Ouabain was administered to the perfusate and, when the EP reached 0 mV, both ouabain and bumetanide were administered.
  
  
  RESULTS
  Although there was no enlargement of the intrastrial space, vacuoles were apparent in marginal cells. The vacuolar change in marginal cells was similar to that caused by ouabain alone.
  
  
  CONCLUSIONS
  This study indicates that the enlargement of the intrastrial space requires not only the blockade of the Na+-K+-2Cl- cotransporter but also normal activity of the Na+-K+-ATPase, and suggests that the bumetanide-induced enlargement of the intrastrial space resulted from the imbalance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase.
authors.affiliation: Department of Otolaryngology, Kochi Medical School, Nankoku, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
authors.forename: Shunji
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Kasumi
authors.initials: K
authors.lastname: Higashiyama
authors.forename: Motonori
authors.initials: M
authors.lastname: Ando
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kakigi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Nakahira
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Taizo
authors.initials: T
authors.lastname: Takeda
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D008854:Microscopy, Electron; D010042:Ouabain / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013316:Stria Vascularis / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004232:Diuretics; D004791:Enzyme Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase