29/04/2015

Endogenousandexogenouscardiacglycosides:theirrolesinhypertension,saltmetabolism,andcellgrowth.PubMedNCBI

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AmJPhysiolCellPhysiol.2007Aug293(2):C50936.Epub2007May9.

Endogenousandexogenouscardiacglycosides:theirrolesin
hypertension,saltmetabolism,andcellgrowth.
SchonerW1,ScheinerBobisG.

Authorinformation
1

InstitutfrBiochemieundEndokrinologie,FachbereichVeterinrmedizin,JustusLiebig
UniversittGiessen,FrankfurterStr100,Giessen,Germany.wilhelm.schoner@vetmed.uni
giessen.de

Abstract
Cardiotonicsteroids(CTS),longusedtotreatheartfailure,areendogenouslyproducedin
mammals.Amongthemarethehydrophiliccardenolideouabainandthemorehydrophobic
cardenolidedigoxin,aswellasthebufadienolidesmarinobufageninandtelecinobufagin.The
physiologicaleffectsofendogenousouabainonbloodpressureandcardiacactivityare
consistentwiththe"Na(+)lag"hypothesis.Thishypothesisassumesthat,incardiacandarterial
myocytes,aCTSinducedlocalincreaseofNa(+)concentrationduetoinhibitionofNa(+)/K(+)
ATPaseleadstoanincreaseofintracellularCa(2+)concentration([Ca(2+)](i))viaabackward
runningNa(+)/Ca(2+)exchanger.Theincreasein[Ca(2+)](i)thenactivatesmusclecontraction.
TheNa(+)laghypothesismaybestexplainshorttermandinotropicactionsofCTS.Yetalldata
ontheCTSinducedalterationofgeneexpressionareconsistentwithanotherhypothesis,based
ontheNa(+)/K(+)ATPase"signalosome,"thatdescribestheinteractionofcardiacglycosides
withtheNa(+)pumpasmachineryactivatingvarioussignalingpathwaysviaintramembraneand
cytosolicproteinproteininteractions.Thesepathways,whichmaybeactivatedsimultaneouslyor
selectively,elevate[Ca(2+)](i),activateSrcandtheERK1/2kinasepathways,andactivate
phosphoinositide3kinaseandproteinkinaseB(Akt),NFkappaB,andreactiveoxygenspecies.
Arecentdevelopmentindicatesthatnewpharmaceuticalswithantihypertensiveandanticancer
activitiesmaybefoundamongCTSandtheirderivatives:theantihypertensiverostafuroxin
suppressesNa(+)resorptionandtheSrcepidermalgrowthfactorreceptorERKpathwayin
kidneytubulecells.Itmaybetheparentcompoundofanewprincipleofantihypertensive
therapy.BufalinandoleandrinorthecardenolideanalogUNBS1450blocktumorcell
proliferationandinduceapoptosisatlowconcentrationsintumorswithconstitutiveactivationof
NFkappaB.
PMID:17494630[PubMedindexedforMEDLINE]

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Endogenousandexogenouscardiacglycosides:theirrolesinhypertension,saltmetabolism,andcellgrowth.PubMedNCBI

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