Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

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

2009; Wiley; Volume: 158; Issue: 2 Linguagem: Inglês

10.1111/j.1476-5381.2009.00329.x

1476-5381

Andréa Rodrigues da Costa, Laila Brito Torres, Emiliano Medei, Rafael A. Ricardo, Jerônimo Pereira de França, Soraya S. Smaili, José Nascimento, Maria E.M. Oshiro, José Wilson Magalhães Bassani, Alice T. Ferreira, Paulo José Ferreira Tucci,

Heart Failure Treatment and Management

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 µmol·L −1 ) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 µmol·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.