oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles
oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles
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DOI：
10.1152/ajpheart.2000.278.1.h175
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发表时间：
2000-01-01
影响因子：
4.8
通讯作者：
Kuo, L
中科院分区：
文献类型：
--
作者：
Hein, TW;Liao, JC;Kuo, L
我们之前的研究表明，氧化低密度脂蛋白（oxLDL），一种假定的致动脉粥样硬化剂，损害内皮依赖性，一氧化氮（NO）介导的离体冠状动脉扩张到药物激动剂。然而，目前尚不清楚oxLDL是否会特异性影响no介导的舒张或一般损害内皮依赖功能，包括超极化因子的释放。在这方面，我们研究了分离的猪冠状动脉（50- 100 μ m管径）在oxLDL （0.5 mg：蛋白质/ml， 60分钟）管腔内孵育前后对各种内皮依赖通路激活的反应。在缺乏oxLDL的情况下，所有血管都出现基底张力和扩张，以响应NO合酶（通过流动和腺苷）、环加氧酶（通过花生四烯酸）、细胞色素P-450单加氧酶（通过缓激肽）和内皮膜超极化（通过蔗糖诱导的高渗透压）的激活。与oxLDL孵育血管60分钟没有改变基底张力，但确实抑制了血流和腺苷增加的血管舒张反应，其方式与NO合成酶抑制剂ng -硝基- l -精氨酸甲酯相似。用载体溶液或天然LDL （0.5 mg蛋白/ml， 60分钟）对血管进行腔内孵育，对血流和腺苷反应的血管舒张没有影响。与no介导的反应相反，由内皮超极化介导的高渗血管舒张不受oxLDL的影响。对环氧合酶激活剂花生四烯酸的内皮依赖性扩张和对细胞色素P-450单氧合酶激活剂缓激肽的内皮依赖性扩张以及对硝普钠的内皮依赖性血管扩张也未被oxLDL改变。总的来说，这些结果；表明oxLDL对内皮依赖性扩张具有选择性作用，对no介导的反应具有特异性损伤，而环加氧酶和细胞色素P-450单加氧酶介导的扩张则不受这种抑制作用的影响。此外，oxLDL似乎不影响内皮细胞超极化介导的血管舒张。
Our previous studies implicated thatoxidized low-density lipoprotein (oxLDL), a putative atherogenic agent, impairs endothelium-dependent, nitric Oxide (NO)-mediated dilation of isolated coronary arterioles to-pharmacological agonists. However, it is not known whether oxLDL specifically affects NO-mediated dilation-or: generally impairs endothelium-dependent function, including the release of hyperpolarizing factors. In this regard, we investigated the dilation of isolated porcine coronary arterioles (50- to 100-mu m luminal diameter) in response to the activation of various endothelium-dependent pathways before and after intraluminal incubation of the vessels with oxLDL (0.5 mg: protein/ml for 60 min). In the absence of oxLDL, all vessels developed basal tone and dilated in response to the activation of NO synthase (by flow and adenosine), :cyclooxygenase (by arachidonic acid), cytochrome P-450 monooxygenase (by bradykinin), and endothelial membrane hyperpolarization (by sucrose-induced hyperosmolarity). Incubation of the vessels with oxLDL for 60 min did not alter basal tone but did inhibit the vasodilatory responses to increased flow and adenosine in a manner similar to that of the NO synthase inhibitor NG-nitro-L-arginine methyl ester. Vasodilations in response to flow and adenosine were not affected by intraluminal incubation of the vessels with either a vehicle solution or the native LDL (0.5 mg protein/ml, 60 min). In contrast with the NO-mediated response, hyperosmotic vasodilation mediated by endothelial hyperpolarization was not affected:by oxLDL. Endothelium-dependent dilations to the cyclooxygenase activator arachidonic acid and to the cytochrome P-450 monooxygenase activator bradykinin and endothelium-independent vasodilation to sodium nitroprusside were also not altered by oxLDL. Collectively, these results;indicate that oxLDL has a selective effect on endothelium-dependent dilation with specific impairment of the NO-mediated :response, whereas cyclooxygenase and cytochrome P-450 monooxygenase-mediated dilations are spared from this inhibitory effect. In addition, oxLDL does not appear to:affect vasodilation mediated by hyperpolarization of the endothelium.