Acrolein generation stimulates hypercontraction in isolated human blood vessels
Acrolein generation stimulates hypercontraction in isolated human blood vessels
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DOI：
10.1016/j.taap.2006.09.009
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发表时间：
2006-12-15
影响因子：
3.8
通讯作者：
Boor, P. J.
中科院分区：
文献类型：
--
作者：
Conklin, D. J.;Bhatnagar, A.;Boor, P. J.
血管痉挛（一种自发性的过度收缩）的风险增加与动脉粥样硬化、吸烟和高血压有关，所有这些情况都涉及氧化应激、脂质过氧化和炎症。检测脂质过氧化和炎症衍生的醛的作用。丙烯醛在人血管痉挛中的作用，我们使用人冠状动脉旁路移植物（CABG）血管和已证实的丙烯醛前体烯丙胺开发了离体模型。烯丙胺以氨基脲敏感性胺氧化酶活性（SSAO）依赖的方式诱导离体大鼠冠状动脉过度收缩。离体人CABG血管（1）血管对丙烯醛、烯丙胺和H2 O2暴露的反应和敏感性（1 μ M-1 mM），（2）使用SSAO抑制剂的烯丙胺诱导效应的SSAO依赖性（氨基脲，1 mM; MDL 72274-E，活性异构体; MDL 72274-Z，非活性异构体; 100 μ M），（3）两种其他SSAO胺底物，苄胺和甲胺的血管活性作用，和（4）细胞外Ca 2+对过度收缩的贡献。丙烯醛或烯丙胺（但不是H2 O2、苄胺或甲胺）会刺激冠状动脉旁路移植术血管中自发且药理学上难以治疗的过度收缩，这与临床血管痉挛相似。用氨基脲或MDL 72274-E预处理可消除烯丙胺引起的过度收缩和血管SSAO活性，但MDL 72274-Z不能。在无钙缓冲液中，烯丙胺诱导的过度收缩也显著减弱。在自发性高血压大鼠离体主动脉，烯丙胺引起SSAO依赖性收缩和去甲肾上腺素敏感性增加，但在Sprague-Dawley大鼠主动脉不引起。我们的结论是，丙烯醛在血管壁中的产生增加了人类对血管痉挛的易感性，血管痉挛是高血压中增强的事件。(c)2006年爱思唯尔公司All rights reserved.
Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde. acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H2O2 exposure (1 mu M-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 mu M), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca2+ to hypercontraction. Acrolein or allylamine but not H2O2, benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca2+-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension. (c) 2006 Elsevier Inc. All rights reserved.