title: Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium.
abstract: Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2+)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2+) 100-1000μM. The contractile response to Ca(2+) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2+) whereas O2(-) was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2+) influx were impaired only by Fe(2+) 1000μM, and antioxidants had no effect. In skinned fibers, Fe(2+) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2+) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000μM, Fe(2+) appears to depress force also by reducing Ca(2+) influx, probably due to a competition at Ca(2+) channels.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria, Brazil.
authors.forename: Renata Andrade
authors.initials: RA
authors.lastname: Ávila
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria, Brazil.
authors.forename: Marito Afonso Sousa Costa
authors.initials: MASC
authors.lastname: Silva
authors.affiliation: Department of Physiology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: João Victor
authors.initials: JV
authors.lastname: Peixoto
authors.affiliation: Department of Physiology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Ilana
authors.initials: I
authors.lastname: Kassouf-Silva
authors.affiliation: Department of Physiology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Rosalvo T H
authors.initials: RTH
authors.lastname: Fogaça
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria, Brazil. Electronic address: leodossantos@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Dos Santos
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology*; D066298:In Vitro Techniques; D019190:Iron Overload / Q000378:metabolism / Q000503:physiopathology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009218:Myosins / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005296:Ferrous Compounds; D017382:Reactive Oxygen Species; D009218:Myosins; D002118:Calcium
keywords: Excitation-contraction coupling; Iron intoxication; Iron poisoning; Papillary muscle; Skinned fiber