Rubanyi G M
Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
J Cell Biochem. 1991 May;46(1):27-36. doi: 10.1002/jcb.240460106.
Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
过去十年的重要发现表明，内皮细胞可通过合成/释放强效血管舒张因子（内皮源性舒张因子；EDRF）和血管收缩物质（内皮源性收缩因子；EDCF）来调节其下方血管平滑肌的张力。显而易见，这些物质的合成与释放有助于血管内皮细胞发挥多种生理功能。越来越多的证据表明，至少有一种EDRF与一氧化氮（NO）或一种不稳定的亚硝基化合物相同，后者由L-精氨酸通过一种依赖NADPH和Ca(2+)的酶——精氨酸氧化酶生成。有人提出存在一种以上化学性质不同的EDRF，包括一种内皮源性超极化因子（EDHF）。EDRF（NO）的作用靶点是可溶性鸟苷酸环化酶（使环磷酸鸟苷增加），而EDHF似乎能激活血管平滑肌中的钾通道。最近的数据表明，毒蕈碱受体亚型可选择性地介导EDRF（NO）（M2）和EDHF（M1）的释放。EDRF（NO）不仅会影响其下方的血管平滑肌，还会影响血小板，抑制其聚集和与内皮细胞的黏附。EDRF的抗聚集作用与前列环素具有协同性，因此它们的联合释放可能代表一种旨在防止血栓形成的生理机制。EDRF（NO）的另一个推测的生物学功能是通过清除超氧阴离子自由基实现细胞保护。内皮细胞还可通过释放多种内皮源性收缩因子（EDCF）来介导血管收缩。除了独特的肽类内皮素外，EDCF的性质尚未完全明确。脑和肾血流量的自身调节以及低氧性肺血管收缩可能代表内皮依赖性血管收缩的生理作用。越来越多的证据表明，内皮细胞可作为一种独特的机械感受器，通过释放EDRF或EDCF将物理刺激（如剪切力、压力）感知并转化为血管张力的变化。在生理状态下，内皮源性血管舒张剂和血管收缩剂之间存在微妙的平衡。这种平衡的改变可导致局部（血管痉挛）和全身性（高血压）血管张力增加，还会促进血栓形成。内皮功能障碍也可能与高胆固醇血症和动脉粥样硬化相关的血管病变的病理生理学有关。
