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Differential actions of eplerenone and spironolactone on the protective effect of testosterone against cardiomyocyte apoptosis in vitro

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Efecto diferencial de espironolactona frente a eplerenona sobre el papel protector in vitro de testosterona en la apoptosis de cardio.pdf(150.58 KB)
Date
2010-07
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Authors
Sanchez-Mas, Jesus ; Turpin, Maria C ; Lax Pérez, Antonio Manuel ; Ruiperez, Juan A ; Valdes Chavarri, Mariano ; Pascual Figal, Domingo A.
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Medicina
DOI
10.1016/s1885-5857(10)70162-6
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info:eu-repo/semantics/article
Description
©2010. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Revista Española de cardiología. To access the final edited and published work see https://doi.org/10.1016/s1885-5857(10)70162-6
Abstract
Introduction and objectives: Testosterone deficiency is associated with a poor prognosis in patients with heart failure. It is not clear whether testosterone reduces cardiomyocyte apoptosis or whether the effect of spironolactone, an aldosterone receptor blocker with progestogenic and anti-androgen activity, differs from that of the selective aldosterone blocker eplerenone. Methods: Apoptosis induced by hyperosmotic stress in the embryonic rat heart cell line H9c2 was monitored by measuring cell viability, DNA fragmentation and caspase-3, -8 and -9 activation. The effect of testosterone was investigated in the presence or absence of spironolactone and eplerenone. Results: Exposure to sorbitol (0.6 M, 3 h) decreased cell viability and increased DNA fragmentation and caspase-3, -8 and -9 activation. These effects were all significantly reduced by testosterone, 100 nM (P< .01). Pretreatment with spironolactone, 10 .M, blocked the effects of testosterone, decreased cell viability (P< .01) and increased caspase activation (P< .01). In contrast, eplerenone, 10 .M, increased cell viability (P< .001) without altering the effect on caspase activation. These actions were not modified by the androgen receptor blocker flutamide. They were mediated by SAPK/JNK and ERK1/2 signaling pathways (P< .01). Conclusions: Testosterone appears to have a protective effect against cardiomyocyte apoptosis which is antagonized by spironolactone but not by eplerenone. These effects await confirmation in in vivo models, but their presence could have clinical and therapeutic implications.
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Apoptosis , Antagonistas de aldosterona , Testosterona , Línea celular cardiaca.
Citation
Rev Esp Cardiol. 2010 Jul 63(7):779-87.
URI
http://hdl.handle.net/10201/137589
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