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Type: Artigo de periódico
Title: The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients
Author: Costa, AR
Torres, LB
Medei, E
Ricardo, RA
Franca, JP
Smaili, S
Nascimento, JHM
Oshiro, MEM
Bassani, JWM
Ferreira, AT
Tucci, PJF
Abstract: 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.
Subject: spironolactone
calcium channel
sarcoplasmic reticulum
Country: EUA
Editor: Wiley-blackwell Publishing, Inc
Citation: British Journal Of Pharmacology. Wiley-blackwell Publishing, Inc, v. 158, n. 2, n. 580, n. 587, 2009.
Rights: fechado
Identifier DOI: 10.1111/j.1476-5381.2009.00329.x
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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