Spieker L E, Noll G, Ruschitzka F T, Maier W, Lüscher T F
Cardiology, University Hospital, Zürich, Switzerland.
J Hum Hypertens. 2000 Oct-Nov;14(10-11):617-30. doi: 10.1038/sj.jhh.1001012.
The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxidative stress plays an important role in the pathogenesis of hypertension. Superoxide anions, ie, oxygen radicals produced in part by angiotensin II-activated NAD(P)H oxidase, can scavenge NO to form peroxynitrite, which can nitrosylate membrane proteins and oxidize lipids. Another source of superoxide is cyclooxygenase. Paradoxically, dysfunctional endothelial NO synthase may also be a source of superoxide anions. Surprisingly and in contrast to animal experiments, not all antihypertensive treatments consistently restore endothelium-dependent vasodilation in patients with arterial hypertension. Endothelial dysfunction in hypertension is crucial both for the development of the disease process in the vasculature and an important therapeutic target.
血管内皮细胞合成并释放一系列血管活性物质，如一氧化氮（NO）和内皮素（ET）。在高血压中，内皮源性因子的微妙平衡被打破。ET是内皮源性NO的天然对应物，NO具有血管舒张、抗血栓形成和抗增殖作用，并抑制白细胞与血管壁的粘附。除了在人体中也有升高血压的作用外，ET还可诱导血管和心肌肥大，而这是心血管发病和死亡的独立危险因素。高血压中内皮功能紊乱可能部分由遗传因素引起，但也与血压本身升高有关。由于内皮细胞位于血压与负责外周阻力的平滑肌细胞之间，因此被认为既是动脉高血压的靶器官，也是其介导者。氧化应激在高血压发病机制中起重要作用。超氧阴离子，即部分由血管紧张素II激活的NAD(P)H氧化酶产生的氧自由基，可清除NO以形成过氧亚硝酸盐，而过氧亚硝酸盐可使膜蛋白亚硝化并氧化脂质。超氧阴离子的另一个来源是环氧化酶。矛盾的是，功能失调的内皮型NO合酶也可能是超氧阴离子的来源。令人惊讶的是，与动物实验不同，并非所有抗高血压治疗都能持续恢复动脉高血压患者的内皮依赖性血管舒张。高血压中的内皮功能障碍对于血管系统疾病进程的发展至关重要，也是一个重要的治疗靶点。
