简介：Overthepasttwodecadesconsiderableprogresshasbeenmadeinunderstandingtheototoxiceffectsandmechanismsunderlyingloopdiuretics.Astypicalrepresentativeofloopdiureticsethacrynicacidorfurosemideonlyinducestemporaryhearingloss,butrarelypermanentdeafnessunlessappliedinsevereacuteorchronicrenalfailureorwithotherototoxicdrugs.Loopdiureticinduceuniquepathologicalchangesinthecochleasuchasformationofedematousspacesintheepitheliumofthestriavascularis,whichleadstorapiddecreaseoftheendolymphaticpotentialandeventuallossofthecochlearmicrophonicpotential,summatingpotential,andcompoundactionpotential.LoopdiureticsinterferewithstrialadenylatecyclaseandNat/Kt-ATPaseandinhibittheNa-K-2Clcotransporterinthestriavascularis,howeverrecentreportsindicatethatoneoftheearliesteffectsinvivoistoabolishbloodflowinthevesselssupplyingthelateralwall.Sinceethacrynicaciddoesnotdamagethestriavascularisinvitro,thechangesinNat/Kt-ATPaseandNa-K-2Clseeninvivomaybesecondaryeffectsresultsfromstrialischemiaandanoxia.Recentobservationsshowingthatreninispresentinpericytessurroundingstriaarteriolessuggestthatdiureticsmayinducelocalvasoconstrictionbyreninsecretionandangiotensinformation.Thetightjunctionsintheblood-cochleabarrierpreventtoxicmoleculesandpathogensfromenteringcochlea,butwhendiureticsinduceatransientischemia,thebarrieristemporarilydisruptedallowingtheentryoftoxicchemicalsorpathogens.