Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro
Open access
Datum
2012Typ
- Journal Article
ETH Bibliographie
yes
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Abstract
Sodium nitroprusside (SNP) is used clini-cally as a rapid-acting vasodilator and in exper-imental models as donor of nitric oxide (NO).High concentrations of NO have been reportedto induce cardiotoxic effects including apopto-sis by the formation of reactive oxygen species.We have therefore investigated effects of SNPon the myofibrillar cytoskeleton, contractilityand cell death in long-term cultured adult ratcardiomyocytes at different time points aftertreatment. Our results show, that SNP treat-ment at first results in a gradual increase ofcytoskeleton degradation marked by the loss ofactin labeling and fragmentation of sarcomer-ic structure, followed by the appearance ofTUNEL-positive nuclei. Already lower doses ofSNP decreased contractility of cardiomyocytespaced at 2 Hz without changes of intracellularcalcium concentration. Ultrastructural analy-sis of the cultured cells demonstrated mito-chondrial changes and disintegration of sar-comeric alignment. These adverse effects ofSNP in cardiomyocytes were reminiscent ofanthracycline-induced cardiotoxicity, whichalso involves a dysregulation of NO with theconsequence of myofibrillar degradation andultimately cell death. An inhibition of the path-ways leading to the generation of reactive NOproducts, or their neutralization, may be of sig-nificant therapeutic benefit for both SNP andanthracycline-induced cardiotoxicity. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000050371Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
European Journal of HistochemistryBand
Seiten / Artikelnummer
Verlag
PAGEPressThema
Cardiomyocytes; Anthracyclines; Nitric oxide; Apoptosis; Reactive oxygen speciesETH Bibliographie
yes
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