[Hypertension, endothelial dysfunction and cardiovascular risk].
[Hypertension, endothelial dysfunction and cardiovascular risk].
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[高血压、内皮功能障碍和心血管风险]。
DOI：
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
A. Nitenberg
中科院分区：
文献类型：
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作者：
A. Nitenberg
血压升高引起血管内皮的功能和结构改变。内皮依赖性血管舒张抑制是高血压引起的内皮功能障碍的早期表现。它可以通过药理学或生理学试验来证明。一氧化氮（NO）可用性降低是血管舒张抑制的主要决定因素。这可能是由于no -内皮合成酶（NOSe）活性的降低与以下因素有关：1)底物（l -精氨酸）的缺陷，2)不对称二甲基精氨酸的抑制，3)辅助因子四氢生物蝶呤（BH4）的缺陷。然而，氧化应激的增加是决定性因素，氧化应激是一种超氧自由基的生产者，它与NO结合形成过氧硝酸盐（ONOO-）。这与激活蛋白C激酶的机械传感器的刺激引起的膜性NAD(P)H氧化酶的激活有关。这一信息被BH4的氧化放大，BH4将NOSe转化为超氧化物自由基的制造者。一连串的自动扩增循环会导致动脉粥样硬化及其并发症。超氧自由基和过氧硝酸盐氧化低密度脂蛋白胆固醇。它们激活核因子- kappab，该因子控制刺激许多蛋白质表达的基因：刺激交感神经系统的血管紧张素原和AT1受体、氧化LDL受体、粘附和迁移因子（ICAM-1、VCAM-1、e -选择素和MCP-1）、促炎细胞因子（白介素和tnf - α）、生长因子（MAP激酶）、纤溶酶原激活物抑制剂1。单核细胞和平滑肌细胞产生金属蛋白酶和促炎细胞因子，使动脉粥样硬化斑块不稳定，有利于血管重构。总之，高血压引起的内皮功能障碍是一个复杂的生理病理过程，是未来心血管事件的标志。
Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.