IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IN RABBIT RENAL-ARTERIES BY OXIDIZED LIPOPROTEIN(A) - ROLE OF OXYGEN-DERIVED RADICALS
IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IN RABBIT RENAL-ARTERIES BY OXIDIZED LIPOPROTEIN(A) - ROLE OF OXYGEN-DERIVED RADICALS
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DOI：
10.1161/01.cir.92.6.1582
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发表时间：
1995-09-15
期刊：
影响因子：
37.8
通讯作者：
WANNER, C
中科院分区：
文献类型：
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作者：
GALLE, J;BENGEN, J;WANNER, C
背景 高脂蛋白血症与一氧化氮 (NO) 介导的、内皮依赖性肾动脉扩张受损有关。在本研究中，我们在体外评估和比较了人脂蛋白（a）和低密度脂蛋白（LDL）对内皮依赖性和非依赖性扩张的影响。方法和结果通过光电装置在分离的、灌注盐水的、预收缩的动脉段中检测扩张器反应。与天然脂蛋白(a)（30和100μg/mL）孵育150分钟后，乙酰胆碱诱导的兔肾动脉内皮依赖性扩张剂反应没有显着减弱。然而，暴露于体外氧化脂蛋白(a)（150分钟、30和100μg/mL）以剂量依赖性方式抑制乙酰胆碱诱导的扩张器反应。在相似浓度下，天然低密度脂蛋白和氧化低密度脂蛋白没有影响。 NO供体硝普钠诱导的内皮依赖性扩张也受到氧化脂蛋白(a)的损害，而毛喉素诱导的扩张反应不受影响，表明平滑肌扩张能力未受损。超氧化物歧化酶 (SOD) 存在时，氧化脂蛋白 (a) 对扩张剂反应的减弱作用会增强。与过氧化氢酶 (100 U/mL) 或去铁胺共孵育可完全减弱 SOD 的作用。在缺乏 SOD 的情况下，过氧化氢酶或去铁胺对扩张剂反应没有影响。使用化学发光测定法，我们可以检测到用氧化脂蛋白(a)预处理的动脉产生的O-2(-)增加，这表明O-2(-)增强的NO失活可能是损害内皮依赖性扩张的潜在机制。结论这些数据表明，氧化脂蛋白(a)损害内皮依赖性扩张，并且在这种作用上比氧化LDL更有效。损伤机制可能涉及O-2(-)的形成和NO的失活。
Background Hyperlipoproteinemia is associated with impairment of nitric oxide (NO)-mediated, endothelium-dependent dilation in renal arteries. In the present study, we assessed and compared the effects of human Lipoprotein(a) and LDL on endothelium-dependent and -independent dilation in vitro.Methods and Results Dilator responses were detected in isolated, saline-perfused, preconstricted arterial segments by a photoelectric device. Acetylcholine-induced, endothelium-dependent dilator responses of rabbit renal arteries were not significantly attenuated after 150 minutes of incubation with native lipoprotein(a) (30 and 100 mu g/mL). However, exposure to in vitro oxidized lipoprotein(a) (150 minutes, 30 and 100 mu g/mL) suppressed acetylcholine-induced dilator responses in a dose-dependent manner. At similar concentrations, native and oxidized LDL had no effect. Endothelium-independent dilations induced by the NO-donor sodium nitroprusside were also impaired by oxidized lipoprotein(a), whereas forskolin-induced dilator responses were unaffected, indicating that smooth muscle dilator capacity was not impaired. Attenuation of dilator responses by oxidized lipoprotein(a) was potentiated in the presence of superoxide dismutase (SOD). The SOD effect was completely blunted by coincubation with catalase (100 U/mL) or deferoxamine. In the absence of SOD, catalase or deferoxamine had no effect on dilator responses. Using a chemiluminescence assay, we could detect increased O-2(-) production by arteries pretreated with oxidized lipoprotein(a), which suggested that enhanced NO inactivation by O-2(-) could be the underlying mechanism for impairment of endothelium-dependent dilations.Conclusions These data indicate that oxidized lipoprotein(a) impairs endothelium-dependent dilation and is more potent than oxidized LDL in this effect. The mechanism of the impairment may involve formation of O-2(-) and inactivation of NO.