Kuang Wei, Chen Ying-Ying, Shen Yue-Liang, Xia Qiang
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031.
Sheng Li Xue Bao. 2003 Jun 25;55(3):273-7.
The present study was to examine the effect of iron on isolated rat aortic rings, and to elucidate the underlying mechanism. The thoracic aortic rings without endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. The results obtained are as follows. (1) Ferric ammonium citrate (FAC) (100 micromol/L) caused a phasic response with an initial transient contraction followed by a relaxation in thoracic aortic ring. The maximal contractile amplitude was 24.02+/-2.37% of the maximal contraction induced by KCl, the duration of phasic contraction lasted for about 20 min. (2) In high Ca(2+) Krebs-Henseleit (K-H) solution (twice of the normal concentration), the contractile amplitude induced by FAC was enhanced. After the aortic rings were incubated with nifedipine for 15 min to block the L-type Ca(2+) channel, the iron-induced contraction was attenuated. (3) In Ca(2+)-free K-H solution, addition of FAC caused a strong and sustained contraction in the presence of PDBu. (4) Pretreatment of FAC for 30 min decreased the KCl-induced contraction and also caused a significant reduction in the contractile response to phenylephrine (PE). Pretreatment of the arteries with DMSO, catalase or glutathione before FAC exposure prevented the decrease in contraction responses to PE (P<0.05). It is therefore concluded that iron causes phasic contraction of vascular smooth muscle, in which both extracellular Ca(2+) entry through L-type Ca(2+) channel and increase in Ca(2+) sensitivity of smooth muscle cells are involved. Exposure to iron causes inhibitory effects on KCl- or PE-induced contractions in isolated thoracic arteries. Reactive oxygen species and glutathione may be involved in iron-induced contraction dysfunction.
本研究旨在检测铁对分离的大鼠主动脉环的影响，并阐明其潜在机制。将雄性Sprague-Dawley大鼠的无内皮胸主动脉环安装在浴槽系统上。测量主动脉环的等长收缩。所得结果如下：（1）柠檬酸铁铵（FAC，100微摩尔/升）引起阶段性反应，胸主动脉环先出现短暂的初始收缩，随后舒张。最大收缩幅度为氯化钾诱导的最大收缩的24.02±2.37%，阶段性收缩持续约20分钟。（2）在高钙（Ca²⁺）的Krebs-Henseleit（K-H）溶液（正常浓度的两倍）中，FAC诱导的收缩幅度增强。在用硝苯地平孵育主动脉环15分钟以阻断L型Ca²⁺通道后，铁诱导的收缩减弱。（3）在无钙的K-H溶液中，加入FAC在存在佛波醇肉豆蔻酸酯（PDBu）的情况下引起强烈且持续的收缩。（4）FAC预处理30分钟可降低氯化钾诱导的收缩，并使对去氧肾上腺素（PE）的收缩反应显著降低。在暴露于FAC之前用二甲基亚砜、过氧化氢酶或谷胱甘肽预处理动脉可防止对PE的收缩反应降低（P<0.05）。因此得出结论，铁引起血管平滑肌的阶段性收缩，其中涉及通过L型Ca²⁺通道的细胞外Ca²⁺内流和平滑肌细胞Ca²⁺敏感性增加。暴露于铁对分离的胸主动脉中氯化钾或PE诱导的收缩有抑制作用。活性氧和谷胱甘肽可能参与铁诱导的收缩功能障碍。
