Boulanger C M
Inserm Unit 141, University Paris VII, Hopital Lariboisière, France.
J Mol Cell Cardiol. 1999 Jan;31(1):39-49. doi: 10.1006/jmcc.1998.0842.
The endothelium is a major regulator of vascular tone, releasing vasoactive substances such as endothelium-derived nitric oxide (EDRF), endothelium-derived hyperpolarizing factor(s), cycloxygenase metabolites, endothelin and other endothelium-derived contracting factors (EDCF). In a number of cardiovascular pathologies, such as hypertension or heart failure, the balance in the endothelial production of vasodilating and vasoconstricting mediators is altered. The resulting apparent decrease in endothelium-dependent relaxations is termed 'endothelial dysfunction'. In hypertensive patients and in animal models of hypertension, endothelium-dependent relaxations are impaired. However, this endothelial dysfunction presents different characteristics depending on the model studied. In Dahl-salt-sensitive rats, the decrease in endothelium-dependent relaxations is associated with impaired constitutive nitric oxide synthase activity. The presence of an endogenous nitric oxide synthase inhibitor and a decreased response of vascular smooth muscle to the mediator may contribute also to the dysfunction observed in this model. In other animal models of hypertension (such as spontaneous hypertension). the contribution of the L-arginine nitric oxide pathway to endothelium-dependent responses appears normal or impaired despite reports of increased nitric oxide synthase activity or expression. In large arteries from SHR, endothelium-dependent relaxations are impaired mainly because of the concomitant augmented release of endoperoxides activating thromboxane-endoperoxide receptors. Superoxide anions may also play a role in some models, but only in the early phase of the disease: whether or not these species contribute to further development of endothelial dysfunction or to increases in blood pressure remains to be examined. The endothelial dysfunction observed in hypertension is likely to be a consequence of high blood pressure. but it could facilitate the maintenance of elevated peripheral resistance at a later stage in the disease and favour the occurrence of complications, such as atherosclerosis.
内皮是血管张力的主要调节者，可释放血管活性物质，如内皮衍生的一氧化氮（EDRF）、内皮衍生的超极化因子、环氧化酶代谢产物、内皮素及其他内皮衍生的收缩因子（EDCF）。在一些心血管疾病中，如高血压或心力衰竭，内皮产生的血管舒张和血管收缩介质的平衡会发生改变。由此导致的内皮依赖性舒张功能明显下降被称为“内皮功能障碍”。在高血压患者和高血压动物模型中，内皮依赖性舒张功能受损。然而，这种内皮功能障碍根据所研究的模型呈现出不同的特征。在 Dahl 盐敏感大鼠中，内皮依赖性舒张功能的下降与组成型一氧化氮合酶活性受损有关。内源性一氧化氮合酶抑制剂的存在以及血管平滑肌对介质反应的降低也可能导致该模型中观察到的功能障碍。在其他高血压动物模型（如自发性高血压）中，尽管有报道称一氧化氮合酶活性或表达增加，但 L-精氨酸一氧化氮途径对内皮依赖性反应的贡献似乎正常或受损。在自发性高血压大鼠的大动脉中，内皮依赖性舒张功能受损主要是因为同时增加了激活血栓素-内过氧化物受体的内过氧化物的释放。超氧阴离子在某些模型中也可能起作用，但仅在疾病的早期阶段：这些物质是否会导致内皮功能障碍的进一步发展或血压升高仍有待研究。高血压中观察到的内皮功能障碍可能是高血压的结果，但它可能在疾病后期促进外周阻力升高的维持，并有利于并发症的发生，如动脉粥样硬化。
