铁对血管收缩活动的影响及其机制

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) 10 0 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 2 4 0 2± 2 3 7%。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 0 1)。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 0 1)。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 3 0min后 ,KCl引起血管环收缩的幅度显著降低 (P <0 0 1)。铁孵育可使PE引起的收缩量 -效曲线右移 (P <0 0 5 )。 ( 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 0 5 )。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

Effect of iron on vasoconstriction in the isolated rat aorta

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.