Acta Physiologica Sinica, June 25
研究论文
铁对血管收缩活动的影响及其机制
况炜1,2, 陈莹莹1, 沈岳良1, 夏强1,*
1浙江大学医学院生理学教研室, 杭州 310031; 2宁波卫生高等职业技术学院, 宁波 315000
摘要: 动脉粥样硬化的发生和铁引起的氧化应激密切相关。铁对血管的直接效应及其对血管收缩功能的影响尚不明确。本文采用血管环灌流装置, 观察铁对离体SD大鼠去内皮胸主动脉环的直接效应, 及对去内皮主动脉环KCl和苯肾上腺素(PE)引发的收缩效应的影响。结果显示: (1)100 μmol/L 枸橼酸铁(FAC)引起大鼠血管环发生相位性收缩, 最大收缩幅度可达KCl诱发的最大收缩的24.02±2.37%。当[Ca2+]o增加1倍时, 铁所致的血管环收缩幅度明显增加(P<0.01)。阻断L-型钙通道后, 铁所致的血管环收缩幅度明显降低(P<0.01)。在无钙液中, 用佛波酯收缩血管环, 待收缩稳定后给予FAC, 此时收缩幅度增加49.18±3.75%。(2) 铁孵育30 min后, KCl引起血管环收缩的幅度显著降低(P<0.01)。铁孵育可使PE引起的收缩量-效曲线右移(P<0.05)。(3)二甲基亚砜、过氧化氢酶和谷胱甘肽可明显降低铁对PE血管收缩反应的抑制作用(P<0.05)。从这些结果可得到以下结论: 铁可引起胸主动脉发生相位性收缩, 其机制可能与L-型钙通道短暂开放导致钙离子内流, 及平滑肌对钙的敏感性增加有关; 较长时间与铁孵育后, 可对血管收缩功能产生损伤, 氧自由基的生成增加和细胞内GSH的水平降低可能参与铁对收缩功能的损害。
关键词: 铁; 胸主动脉; 收缩; L-型钙通道; 活性氧
中图分类号: Q463
Effect of iron on
vasoconstriction in the isolated rat aorta
KUANG Wei1, 2, CHEN Ying-Ying1, SHEN Yue-Liang1, XIA Qiang1，
1Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031;
2Department of Physiology, Ningbo Health Technical College, Ningbo 315000
Abstract: 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 μmol/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 Ca2+ 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 Ca2+ channel, the iron-induced contraction was attenuated. (3) In Ca2+-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 Ca2+ entry through L-type Ca2+ channel and increase in Ca2+ 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.
Key words: iron; thoracic aorta; vasoconstriction; L-type Ca2+ channel; reactive oxygen species