title: Peroxynitrite-induced cardiac myocyte injury.
abstract: 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.
authors.affiliation: Department of Physiology 2, Tokai University, Isehara, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Ichimori
authors.forename: Y
authors.initials: Y
authors.lastname: Hirota
authors.forename: M
authors.initials: M
authors.lastname: Fukahori
authors.forename: H
authors.initials: H
authors.lastname: Nakazawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D007700:Kinetics; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D009566:Nitrates / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D009566:Nitrates; D017392:Thiobarbituric Acid Reactive Substances; C039642:peroxynitric acid; D002118:Calcium