ENDOTHELIUM-DERIVED RELAXING AND CONTRACTING FACTORS
ENDOTHELIUM-DERIVED RELAXING AND CONTRACTING FACTORS
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DOI：
10.1002/jcb.240460106
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发表时间：
1991-05-01
影响因子：
4
通讯作者：
RUBANYI, GM
中科院分区：
文献类型：
--
作者：
RUBANYI, GM
过去十年的关键发现表明，内皮细胞可以通过合成/释放强效血管舒张剂（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）来调节基础血管平滑肌的张力。很明显，这些物质的合成和释放有助于血管内皮执行多种生理功能。越来越多的证据表明，至少有一个EDRF是相同的一氧化氮（NO）或不稳定的亚硝基化合物，这是从L-精氨酸产生的NADPH和Ca 2+依赖性酶，精氨酸氧化酶。已经提出存在一种以上化学上不同的EDRF，包括内皮源性超极化因子（EDHF）。EDRF（NO）的靶点是可溶性鸟苷酸环化酶（增加环GMP），而EDHF似乎激活血管平滑肌中的K+通道。最近的数据表明，毒蕈碱受体亚型选择性介导EDRF（NO）（M2）和EDHF（M1）的释放。EDRF（NO）不仅影响血管平滑肌，还影响血小板，抑制其聚集和粘附到内皮。EDRF的抗聚集作用与前列环素是协同的，因此它们的联合释放可能代表了旨在防止血栓形成的生理机制。EDRF（NO）的另一种生物学功能是通过清除超氧化物自由基来保护细胞。内皮还可以通过释放多种内皮源性收缩因子（EDCF）来介导血管收缩。除了独特的肽内皮素之外，EDCF的性质尚未明确。脑和肾血流的自动调节和缺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，内皮细胞可以作为一个独特的机械感受器，传感和转导物理刺激（例如，剪切力、压力）通过EDRF或EDCF的释放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（高血压）血管张力增加，并促进血栓形成。内皮功能障碍也可能导致与高胆固醇血症和动脉粥样硬化相关的血管病的病理生理学。
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 Ca2+-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 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.