[page 90] [European Journal of Histochemistry 2012; 56:e15]

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 reported to induce cardiotoxic effects including apopto-sis 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 treat-ment at first results in a gradual increase of cytoskeleton degradation marked by the loss of actin labeling and fragmentation of sarcomer-ic 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 analy-sis of the cultured cells demonstrated mito-chondrial changes and disintegration of sar-comeric 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 path-ways leading to the generation of reactive NO products, or their neutralization, may be of sig-nificant therapeutic benefit for both SNP and anthracycline-induced cardiotoxicity