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N-acetylcysteine prevents electrical remodeling and attenuates cellular hypertrophy in epicardial myocytes of rats with ascending aortic stenosis

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Abstract

Pressure overload is associated with cardiac hypertrophy and electrical remodeling. Here, we investigate the effects of the antioxidant N-acetylcysteine (NAC) on the cellular cardiac electrophysiology of female Sprague–Dawley rats with ascending aortic stenosis (AS). Rats were treated with NAC (1 g/kg body weight) or control solution 1 week before the intervention and in the week following AS or sham operation. Seven days after the operation, blood pressure and left ventricular pressure were measured before the heart was excised. Single cells were isolated from epicardial and endocardial layers of the left ventricular free wall and investigated using the whole-cell patch-clamp technique. Systolic blood pressure and left ventricular peak pressure were not significantly altered in the NAC group. NAC reduced the increase (p < 0.001) in the relative left ventricular weight (p < 0.05) as well as the increase (p < 0.001) in cell capacitance in epicardial (p < 0.05), but not in endocardial myocytes of AS animals. The L-type Ca2+ current (I CaL) was significantly increased by AS in epicardial (+19 % at 0 mV, p < 0.01) but not in endocardial myocytes. NAC completely prevented this increase in I CaL (p < 0.01). The current density of the transient outward K+ current (I to) was not affected by AS or NAC. Action potential duration to 90 % repolarization was significantly prolonged in epicardial (p < 0.01) as well as in endocardial (p < 0.001) cells of AS animals. NAC prevented the AP prolongation in epicardial myocytes only (p < 0.05). We conclude that reducing oxidative stress in pressure overload can prevent electrical remodeling and ameliorate hypertrophy in epicardial but not in endocardial myocytes.

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Acknowledgments

We gratefully acknowledge the expert technical assistance of Céline Grüninger. This work was supported by the Johannes und Frieda Marohn-Stiftung.

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  1. Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstraße 6, 91054, Erlangen, Germany

    Wibke U. Foltz, Michael Wagner, Elena Rudakova & Tilmann Volk

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  1. Wibke U. Foltz
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  2. Michael Wagner
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Correspondence to Michael Wagner or Tilmann Volk.

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W. U. Foltz and M. Wagner contributed equally to this work.

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Foltz, W.U., Wagner, M., Rudakova, E. et al. N-acetylcysteine prevents electrical remodeling and attenuates cellular hypertrophy in epicardial myocytes of rats with ascending aortic stenosis. Basic Res Cardiol 107, 290 (2012). https://doi.org/10.1007/s00395-012-0290-4

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