Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity

  • M. Chiusa Bern University Hospital, Switzerland.
  • F. Timolati Bern University Hosptial, Switzerland.
  • J.C. Perriard Federal Institute of Technology, ETHZ, Zürich, Switzerland.
  • T.M. Suter Bern University Hospital, Switzerland.
  • C. Zuppinger | christian.zuppinger@dkf.unibe.ch Bern University Hospital, Switzerland.

Abstract

Sodium nitroprusside (SNP) is used clinically as a rapid-acting vasodilator and in experimental models as donor of nitric oxide (NO). High concentrations of NO have been reported to induce cardiotoxic effects including apoptosis by the formation of reactive oxygen species. We have therefore investigated effects of SNP on the myofibrillar cytoskeleton, contractility and cell death in long-term cultured adult rat cardiomyocytes at different time points after treatment. Our results show, that SNP treatment at first results in a gradual increase of cytoskeleton degradation marked by the loss of actin labeling and fragmentation of sarcomeric structure, followed by the appearance of TUNEL-positive nuclei. Already lower doses of SNP decreased contractility of cardiomyocytes paced at 2 Hz without changes of intracellular calcium concentration. Ultrastructural analysis of the cultured cells demonstrated mitochondrial changes and disintegration of sarcomeric alignment. These adverse effects of SNP in cardiomyocytes were reminiscent of anthracycline-induced cardiotoxicity, which also involves a dysregulation of NO with the consequence of myofibrillar degradation and ultimately cell death. An inhibition of the pathways leading to the generation of reactive NO products, or their neutralization, may be of significant therapeutic benefit for both SNP and anthracycline-induced cardiotoxicity.

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Author Biographies

M. Chiusa, Bern University Hospital

University Hospital Bern, Department Heart and Vessels

Scientist

F. Timolati, Bern University Hosptial

University Hospital Bern, Department Heart and Vessels

Scientist

J.C. Perriard, Federal Institute of Technology, ETHZ, Zürich
ETHZ, professor emeritus
T.M. Suter, Bern University Hospital

University Hospital Bern, Department Heart and Vessels

professor of cardiology

C. Zuppinger, Bern University Hospital

University Hospital Bern, Department Heart and Vessels

Senior Scientist

Published
2012-04-16
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Section
Original Papers
Supporting Agencies
This work was supported by Swiss National Science Foundation grant 3100A0-120664 to C. Zuppinger and a grant of the Gebert-Ruef foundation (GRS 038/01) to J.C. Perriard
Keywords:
cardiomyocytes, anthracyclines, nitric oxide, apoptosis, reactive oxygen species
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How to Cite
Chiusa, M., Timolati, F., Perriard, J., Suter, T., & Zuppinger, C. (2012). Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity. European Journal of Histochemistry, 56(2), e15. https://doi.org/10.4081/ejh.2012.15