Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos

• Autor(a) principal: Marques, Vinícius Bermond
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/8008
• topic: Iron; Vascular reactivity; Reactive oxygen species; Endothelium; Ferro; Aorta; Reatividade vascular; Espécies reativas de oxigênio; Endotélio; Fisiologia; 612

Iron overload in human and animal models increases oxidative stress and induces cardiomyopathy. It has been suggested that vasculature could be damaged by iron overload as well, but impacts on the vascular reactivity and the mechanisms enrolled have not been understood. In this study we aimed to identify possible changes in vascular reactivity of aorta from iron overloaded rats, investigating the underlying mechanisms. Rats were randomized and treated with iron dextran, i.p., 10mg/Kg/day or 100mg/kg/day five days a week for four weeks and compared to a saline injected group (control). Systolic blood pressure was measured weekly by tail cuff plethysmography. At the end of treatment, the blood iron parameters and iron deposition in tissues was assessed, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine, sodium nitroprusside and angiotensin was analyzed in the context of endothelium denudation and incubation with L-NAME, tiron, catalase, apocynin, allopurinol, losartan, indomethacin or SQ 29598. Chronic iron administration increased serum iron and transferrin saturation with significant deposition in the liver. Additionally, high dose iron overload significantly increased the vasoconstrictor response in aortic rings as assessed in vitro, and endothelial denudation or L-NAME incubation have smaller impact on the vascular reactivity of the iron overloaded group, while these parameters have not changed in low dose iron overload group. Nitric oxide sensible fluorescent probe DAF-2 indicated reduced nitric oxide production in moderate iron overload when compared to controls. Iron overload-induced vascular hyperactivity was reversed by incubation with tiron, catalase, apocynin, allopurinol, losartan, indomethacin and SQ 29598. Moreover, malonyldialdehyde was elevated in plasma; and superoxide anion generation and NADPH oxidase membrane-bound subunit (p22phox) expression were increased in aorta from iron-loaded rats. Result demonstrated by the first time that chronic iron overload is associated with altered vascular reactivity with loss of endothelial modulation of the vascular tone. Moreover, the 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 and by way of cyclooxygenase activation.