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

Autor(es):Mostrar menos -

Costa, A. R. ^[1] ; Torres, L. B. ^[2] ; Medei, E. ^[3] ; Ricardo, R. A. ^{[4, 5]} ; Franca, J. P. ^[6] ; Smaili, S. ^[6] ; Nascimento, J. H. M. ^[3] ; Oshiro, M. E. M. ^[6] ; Bassani, J. W. M. ^{[4, 5]} ; Ferreira, A. T. ^[6] ; Tucci, P. J. F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

^[3] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro - Brazil

^[4] Univ Estadual Campinas, Ctr Biomed Engn, Sao Paulo - Brazil

^[5] Univ Estadual Campinas, Dept Biomed Engn, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: British Journal of Pharmacology; v. 158, n. 2, p. 580-587, SEP 2009.
• Citações Web of Science: 7

Resumo

Background 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. (AU)

• Processo FAPESP: 99/04533-4 - Fisiologia e fisiopatologia em cardiologia
• Beneficiário: Paulo Jose Ferreira Tucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 03/14076-7 - Análise morfológica, bioquímica e funcional da musculatura lisa visceral de ratas e camundongos diabéticos
• Beneficiário: Maria Etsuko Miyamoto Oshiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular