Moncada S, Palmer R M, Higgs E A
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Hypertension. 1988 Oct;12(4):365-72. doi: 10.1161/01.hyp.12.4.365.
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent released by vascular endothelium that mediates the relaxation induced by some vasodilators, including acetylcholine and bradykinin. EDRF also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to vascular endothelium. These actions of EDRF are mediated through stimulation of the soluble guanylate cyclase and the consequent elevation of cyclic guanosine 3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient NO is released from endothelial cells to account for the biological activities of EDRF. Organic nitrates exert their vasodilator activity following conversion to NO in vascular smooth muscle cells. Thus, NO may be considered the endogenous nitrovasodilator. NO is synthesized by vascular endothelium from the terminal guanido nitrogen atom(s) of the amino acid L-arginine. This indicates the existence of an enzymic pathway in which L-arginine is the endogenous precursor for the synthesis of NO. The discovery of the release of NO by vascular endothelial cells, the biosynthetic pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysiology of the vessel wall.
内皮源性舒张因子（EDRF）是一种由血管内皮释放的不稳定体液因子，它介导某些血管舒张剂（包括乙酰胆碱和缓激肽）所诱导的血管舒张。EDRF还抑制血小板聚集，诱导聚集血小板解聚，并抑制血小板黏附于血管内皮。EDRF的这些作用是通过刺激可溶性鸟苷酸环化酶以及随后环磷酸鸟苷3',5'-单磷酸水平升高来介导的。EDRF已被鉴定为一氧化氮（NO）。NO和EDRF的药理学特性难以区分；此外，从内皮细胞释放的NO量足以解释EDRF的生物学活性。有机硝酸盐在血管平滑肌细胞中转化为NO后发挥其血管舒张活性。因此，NO可被视为内源性硝基血管舒张剂。NO由血管内皮从氨基酸L-精氨酸的末端胍基氮原子合成。这表明存在一种酶促途径，其中L-精氨酸是合成NO的内源性前体。血管内皮细胞释放NO、导致其生成的生物合成途径及其与其他血管活性物质的相互作用的发现，为血管壁生理和病理生理学的研究开辟了新途径。
