The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients

Página do item simplificado
dc.contributor.authorCosta, A. R. [UNIFESP]
dc.contributor.authorTorres, L. B. [UNIFESP]
dc.contributor.authorMedei, E.
dc.contributor.authorRicardo, R. A.
dc.contributor.authorFrança, Jerônimo Pereira [UNIFESP]
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.authorNascimento, J. H. M.
dc.contributor.authorOshiro, M. E. M. [UNIFESP]
dc.contributor.authorBassani, J. W. M.
dc.contributor.authorFerreira, Alice Teixeira [UNIFESP]
dc.contributor.authorTucci, Paulo José Ferreira [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2016-01-24T13:58:38Z
dc.date.available2016-01-24T13:58:38Z
dc.date.issued2009-09-01
dc.description.abstractBackground and purpose:Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis.Experimental approach:Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca(2+) transients by fluorescence and Ca(2+) fluxes by electrophysiological techniques.Key results:Canrenone (300-600 mu mol center dot L(-1)) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. in cardiomyocytes, canrenone (50 mu mol center dot L(-1)) reduced cell shortening and L-type Ca(2+) channel current, whereas steady-state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca(2+) content of the sarcoplasmic reticulum, intracellular Ca(2+) transient amplitude and intracellular diastolic Ca(2+) concentration. However, the time course of [Ca(2+)](i) decline during transients evoked by caffeine was not affected by canrenone.Conclusion and implications:Canrenone reduced L-type Ca(2+) channel current, amplitude of intracellular Ca(2+) transients and Ca(2+) content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio de Janeiro, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Biomed Engn, São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Ctr Biomed Engn, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo Pesquisa do Estado de São Paulo
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIDFundacao de Amparo Pesquisa do Estado de São Paulo: 99/04533-4
dc.description.sponsorshipIDFundacao de Amparo Pesquisa do Estado de São Paulo: 05/604578
dc.description.sponsorshipIDFundacao de Amparo Pesquisa do Estado de São Paulo: 03/14076-7
dc.description.sponsorshipIDCNPq: 300632/2005-3
dc.description.sponsorshipIDCNPq: 300.692/80-3
dc.format.extent580-587
dc.identifierhttp://dx.doi.org/10.1111/j.1476-5381.2009.00329.x
dc.identifier.citationBritish Journal of Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 158, n. 2, p. 580-587, 2009.
dc.identifier.doi10.1111/j.1476-5381.2009.00329.x
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/31754
dc.identifier.wosWOS:000269676500020
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectspironolactoneen
dc.subjectcanrenoneen
dc.subjectcalciumen
dc.subjectcalcium channelen
dc.subjectsarcoplasmic reticulumen
dc.titleThe negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transientsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos