Marques Vinicius Bermond, Nascimento Tatiani Botelho, Ribeiro Rogério Faustino, Broseghini-Filho Gilson Brás, Rossi Emilly Martinelly, Graceli Jones Bernades, dos Santos Leonardo
Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Department of Morphology, Federal University of Espirito Santo, Vitoria, ES, Brazil.
Life Sci. 2015 Dec 15;143:89-97. doi: 10.1016/j.lfs.2015.10.034. Epub 2015 Oct 30.
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.
Rats were treated with 100mg/kg/day iron-dextran, ip, five days a week for four weeks and compared to a saline-injected group.
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.
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.
动物模型和人类中的铁过载会增加氧化应激并诱发心肌病。有人提出脉管系统也会受到损害，但对血管反应性的影响及其潜在机制仍知之甚少。在本研究中，我们旨在确定铁过载大鼠主动脉血管反应性的可能变化，并研究其潜在机制。
大鼠每周五天腹腔注射100mg/kg/天的右旋糖酐铁，持续四周，并与注射生理盐水的组进行比较。
长期给予铁会增加血清铁和转铁蛋白饱和度，并在肝脏中有大量沉积。此外，体外评估显示，铁过载显著增加了主动脉环的血管收缩反应，内皮剥脱或L-NAME孵育对血管反应性的影响减弱。用DAF-2进行的体外测定表明，铁过载组的一氧化氮生成减少。用替诺、过氧化氢酶、阿朴吗啡、别嘌呤醇和氯沙坦孵育可逆转铁过载诱导的血管活动亢进。此外，铁过载大鼠血浆中的丙二醛升高，主动脉中的超氧阴离子生成和NADPH氧化酶亚基（p22phox）表达增加。
我们的结果表明，慢性铁过载与血管反应性改变以及血管张力的内皮调节丧失有关。这种铁负荷诱导的内皮功能障碍和一氧化氮生物利用度降低可能是活性氧生成增加和局部肾素-血管紧张素系统激活的结果。
