铁抑制血管舒张活动及其作用机制

目的和方法:循环系统内铁的增加可能是导致冠脉粥样硬化病人血管功能损伤的原因之一。然而,目前关于铁对内皮依赖性血管舒张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大鼠胸主动脉环舒张功能的影响。结果:(1)主动脉环用100μmol/L枸橼酸铁(FAC,含Fe³⁺)孵育后,可显著降低乙酰胆碱(ACh)产生的内皮细胞依赖性主动脉环的舒张作用。主动脉环用FAC孵育之前,补充一氧化氮(NO)的前体物质L-精氨酸(L-Arg),ACh(>10^-9mol/L)所致的血管舒张幅度与单纯铁孵育组相比无明显差异。(2)FAC孵育后,L-Arg引起的内皮完整主动脉环舒张幅度显著减小(P<0.05),而无内皮的主动脉环用FAC孵育后,对NO的供体—硝普钠产生的血管舒张作用无明显影响。(3)二甲基亚砜对FAC抑制ACh血管舒张的作用无明显影响;在ACh浓度为(10^-9、10^-6、3×10^-6)mol/L时,过氧化氢酶可显著增加FAC孵育后血管的舒张幅度(P<0.01);还原型谷胱甘肽(GSH)可明显对抗FAC对ACh血管舒张作用的抑制。(4)正常大鼠主动脉环中NOS活性为(56.49±2.49)×10³U/g蛋白,FAC处理组大鼠主动脉环中NOS活性低至(25.15±5.75)×10³U/g蛋白,两者有显著差异(P<0.05)。结论:铁可能通过降低胸

Inhibitory effect of iron on vasodilatation in the isolated rat aorta

AIM: The objectives of the present study were to examine the effect of iron on relaxation of isolated rat aortic rings, and to elucidate the underlying mechanism. METHODS: The thoracic aortic rings of male Sprague-Dawley rats were mounted on bath system. Vasodilatation of aortic rings preconstricted with 10^-6 mol/L of phenylephrine (PE) was measured. RESULTS: (1) Exposure of endothelium-intact aortic rings to ferric ammonium citrate (FAC) for 30 min caused a significant reduction in the relaxation response to acetylcholine (ACh). Pretreatment with L-arginine (L-Arg) before incubation with FAC did not reverse the inhibition of relaxation response to ACh completely. (2) In endothelium-intact aortic rings, L-Arg relaxed the PE preconstricted vessels. Exposure to FAC for 30 min caused the decrease in the relaxation response to L-Arg. There was no difference in the relaxation response to nitric oxide donor, sodium nitroprusside, between endothelium-denuded arteries treated with or without FAC. (3) Dimethyl sulfoxide had no effect on the inhibition of relaxation to ACh by FAC in endothelium-intact rings. Pretreatment of arteries with glutathione and catalase prevented the decrease in relaxation responses to ACh induced by FAC. (4) The nitric oxide synthase activity was (56.49±2.49)×10³U/g protein in normal aorta with endothelium, while after incubation with FAC for 30 min, it reduced to (25.15±5.75)×10³U/g protein ( P< 0.05). CONCLUSION: Inactivation of nitric oxide synthase and decrease in intracellular glutathione level might mediate iron-induced inhibition of arterial relaxation responses to ACh.