Taddei S, Virdis A, Ghiadoni L, Sudano I, Salvetti A
Department of Internal Medicine, University of Pisa, Italy.
J Cardiovasc Pharmacol. 2001 Nov;38 Suppl 2:S11-4. doi: 10.1097/00005344-200111002-00004.
The endothelium can greatly influence vascular tone and structure. The main endothelium-derived factor is nitric oxide (NO), which is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro- and microcirculation and in renal circulation. The mechanism responsible for endothelial alteration in essential hypertensive patients appears to be the activation of an alternative pathway involving cyclooxygenase, which reduces NO availability through production of oxidative stress. In the presence of impaired NO availability a hyperpolarizing factor seems to act as a compensatory pathway to sustain endothelium-dependent relaxation. This compensatory pathway can be further depressed by the simultaneous presence of essential hypertension and hyperhomocysteinaemia, another cardiovascular risk factor causing endothelial dysfunction. Finally, reduced NO availability can increase the biological activity of endothelin-1 because, while in healthy conditions the vasoconstrictor effect of endothelin-1 is partially blunted by endothelial ETB-receptor mediated NO production, in essential hypertensive patients this protective mechanism is lacking on account of impaired NO availability. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium could be a promoter of atherosclerosis and thrombosis and therefore lead to cardiovascular events in essential hypertensive patients.
内皮细胞可极大地影响血管张力和结构。主要的内皮衍生因子是一氧化氮（NO），它不仅是一种强效血管舒张剂，还能抑制血小板聚集、平滑肌细胞增殖、单核细胞黏附和黏附分子表达，从而保护血管壁免受动脉粥样硬化和血栓形成的影响。在人类高血压中，外周和冠状动脉的大、微循环以及肾循环中均已证实存在内皮功能障碍。原发性高血压患者内皮改变的机制似乎是涉及环氧化酶的替代途径的激活，该途径通过产生氧化应激降低NO的可用性。在NO可用性受损的情况下，一种超极化因子似乎作为一种补偿途径来维持内皮依赖性舒张。原发性高血压和高同型半胱氨酸血症（另一种导致内皮功能障碍的心血管危险因素）同时存在可进一步抑制这种补偿途径。最后，NO可用性降低可增加内皮素-1的生物活性，因为在健康状态下，内皮素-1的血管收缩作用会因内皮ETB受体介导的NO产生而部分减弱，而在原发性高血压患者中，由于NO可用性受损，这种保护机制缺失。NO途径的这种改变可能是功能失调的内皮细胞促进动脉粥样硬化和血栓形成并因此导致原发性高血压患者发生心血管事件的主要机制。
