title: Chronic iron overload in rats increases vascular reactivity by increasing oxidative stress and reducing nitric oxide bioavailability.
abstract: OBJECTIVE
  Iron overload in animal models and humans increases oxidative stress and induces cardiomyopathy. It has been suggested that the vasculature is also damaged, but the impacts on vascular reactivity and the underlying mechanisms remain poorly understood. In this study, we aimed to identify possible changes in the vascular reactivity of aortas from iron overloaded rats and investigate the underlying mechanisms.
  
  
  METHODS
  Rats were treated with 100mg/kg/day iron-dextran, ip, five days a week for four weeks and compared to a saline-injected group.
  
  
  RESULTS
  Chronic iron administration increased serum iron and transferrin saturation with significant deposition in the liver. Additionally, iron overload significantly increased the vasoconstrictor response in aortic rings as assessed in vitro, with reduced influence of endothelial denudation or l-NAME incubation on the vascular reactivity. In vitro assay with DAF-2 indicated reduced NO production in the iron overload group. Iron overload-induced vascular hyperactivity was reversed by incubation with tiron, catalase, apocynin, allopurinol and losartan. Moreover, malondialdehyde was elevated in the plasma, and O2(•-) generation and NADPH oxidase subunit (p22phox) expression were increased in the aortas of iron-loaded rats.
  
  
  CONCLUSIONS
  Our results demonstrated that chronic iron overload is associated with altered vascular reactivity and the loss of endothelial modulation of the vascular tone. This iron loading-induced endothelial dysfunction and reduced nitric oxide bioavailability may be a result of increased production of reactive oxygen species and local renin-angiotensin system activation.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Vinicius Bermond
authors.initials: VB
authors.lastname: Marques
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Tatiani Botelho
authors.initials: TB
authors.lastname: Nascimento
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Rogério Faustino
authors.initials: RF
authors.lastname: Ribeiro
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Gilson Brás
authors.initials: GB
authors.lastname: Broseghini-Filho
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Emilly Martinelly
authors.initials: EM
authors.lastname: Rossi
authors.affiliation: Department of Morphology, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Jones Bernades
authors.initials: JB
authors.lastname: Graceli
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. Electronic address: leodossantos@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D001682:Biological Availability; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide
keywords: Endothelium; Haemochromatosis; Iron; Oxidative stress; Vascular disease