Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta
Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta
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DOI：
10.1038/sj.bjp.0702374
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发表时间：
1999-02-01
影响因子：
7.3
通讯作者：
Plane, F
中科院分区：
文献类型：
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作者：
Emsley, AM;Jeremy, JY;Plane, F
1血浆高半胱氨酸（HC）和铜水平升高均与炎性血管疾病（如动脉粥样硬化）的发生有关。在这项研究中，HC和铜的组合对一氧化氮（NO）介导的离体大鼠主动脉环舒张的影响进行了研究。2暴露于HC（10-100 μ M; 30分钟）对乙酰胆碱（ACh; 0.01-10 μ M，n = 4）的舒张没有影响。主动脉环与较高浓度HC的预孵育时间延长（1 mM：180 min）显著抑制内皮依赖性舒张（n=4），但这种抑制作用被铜螯合剂bathocuprione阻止（10 μ M，180分钟，n = 6）。3暴露于HC（100 μ M）和铜（10-100 μ M; 30分钟）导致铜浓度依赖性抑制内皮依赖性舒张（n=4）。这种抑制作用在超氧化物歧化酶（SOD; 100 μ ml（-1）; n=4）或过氧化氢酶（100 μ ml（-1）; n=4）的存在下降低，并进一步降低两种酶的存在（n=5）。4 HC和铜（100 μ M; 30分钟）显着抑制内皮非依赖性舒张甘油三硝酸酯（0.01-10 μ M; n=8）。相比之下，HC（1 mM）单独或与铜（100 μ M）联合使用时，不会抑制内皮非依赖性舒张剂硝普钠（0.01-10 μ M; n=4）的舒张作用。5这些数据表明，铜的存在大大增强了HC对NO介导的离体主动脉环舒张的抑制作用。过氧化氢酶和SOD抑制的减少表明铜催化产生超氧化物和过氧化氢导致内皮源性NO的失活增加或产生减少的可能作用。
1 Elevated plasma levels of homocysteine (HC) and copper have both been associated with the development of inflammatory vascular diseases, such as atherosclerosis. In this study, the effects of a combination of HC and copper on nitric oxide (NO)-mediated relaxation of isolated rat aortic rings were investigated.2 Exposure to HC (10-100 mu M; 30 min) had no effect on relaxation to acetylcholine (ACh; 0.01-10 mu M, n = 4). Pre-incubation of aortic rings with a higher concentration of HC for an extended period (1 mM: 180 min) significantly inhibited endothelium-dependent relaxation (n=4), but this inhibition was prevented by the presence of the copper chelator bathocuprione (10 mu M, 180 min, n = 6).3 Exposure to HC (100 mu M) and copper (10-100 mu M; 30 min) caused a copper concentration-dependent inhibition of endothelium-dependent relaxation (n=4). This inhibitory effect was reduced in the presence of either superoxide dismutase (SOD; 100 u ml(-1); n=4) or catalase (100 u ml(-1); n=4), and further reduced by the presence of both enzymes (n=5).4 HC and copper (100 mu M; 30 min) significantly inhibited endothelium-independent relaxation to glyceryl trinitrate (0.01-10 mu M; n=8). In contrast, HC (1 mM), alone or in combination with copper (100 mu M), did not inhibit relaxation to the endothelium-independent relaxant sodium nitroprusside (0.01-10 mu M; n=4).5 These data indicate that the presence of copper greatly enhances the inhibitory actions of HC on NO-mediated relaxation of isolated aortic rings. The reduction of inhibition by catalase and SOD indicates a possible role for copper-catalyzed generation of superoxide and hydrogen peroxide leading to an increased inactivation or decreased production of endothelium-derived NO.