Peroxynitrite-induced cardiac myocyte injury

Free Radic Biol Med. 1996;20(3):343-50. doi: 10.1016/0891-5849(96)02060-6.


The effects of peroxynitrite (ONOO-) on cultured cardiac myocytes were examined by simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and contractile function. On exposure to 0.2 mM ONOO-, [Ca2+]i increased to beyond the systolic level within 5 min with a concomitant decrease in spontaneous contraction of myocytes followed by complete arrest. Addition of a L-type Ca2+ channel blocker or removal of extracellular Ca2+ prevented the ONOO(-)-induced increase in [Ca2+]i, indicating that the increase in [Ca2+]i was caused by the enhanced influx of Ca2+ through the plasma membrane and not by the enhanced release from sarcoplasmic reticulum (SR). Plasma membrane fluidity and concentration of the thiobarbiturate acid-reactive substance (TBARS) in the cells remained unchanged by the ONOO- treatment. The complete cessation of contraction of myocytes persisted even under the massive increase in [Ca2+]i, which was induced by an additional saponin (5 microM) treatment. In conclusion, ONOO- increases [Ca2+]i in myocytes through disturbance of Ca2+ transport systems in the plasma membrane and impairs contractile protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Calcium / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Cells, Cultured
  • Embryo, Mammalian
  • Heart / drug effects*
  • Heart Ventricles
  • Kinetics
  • Membrane Fluidity / drug effects
  • Mice
  • Myocardial Contraction / drug effects*
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Nitrates / pharmacology*
  • Thiobarbituric Acid Reactive Substances / analysis


  • Nitrates
  • Thiobarbituric Acid Reactive Substances
  • peroxynitric acid
  • Calcium