Ignarro L J, Byrns R E, Buga G M, Wood K S
Department of Pharmacology, University of California Los Angeles, School of Medicine 90024.
Circ Res. 1987 Dec;61(6):866-79. doi: 10.1161/01.res.61.6.866.
The objective of this study was to elucidate the close similarity in properties between endothelium-derived relaxing factor (EDRF) and nitric oxide radical (NO). Whenever possible, a comparison was also made between arterial and venous EDRF. In vascular relaxation experiments, acetylcholine and bradykinin were used as endothelium-dependent relaxants of isolated rings of bovine intrapulmonary artery and vein, respectively, and NO was used to relax endothelium-denuded rings. Oxyhemoglobin produced virtually identical concentration-dependent inhibitory effects on both endothelium-dependent and NO-elicited relaxation. Oxyhemoglobin and oxymyoglobin lowered cyclic guanosine monophosphate (cGMP) levels, increased tone in unrubbed artery and vein, and abolished the marked accumulation of vascular cGMP caused both by endothelium-dependent relaxants and by NO. The marked inhibitory effects of oxyhemoglobin on arterial and venous relaxant responses and cGMP accumulation as well as its contractile effects were abolished or reversed by carbon monoxide. These observations indicate that EDRF and NO possess identical properties in their interactions with oxyhemoproteins. Both EDRF from artery and vein and NO activated purified soluble guanylate cyclase by heme-dependent mechanisms, thereby revealing an additional similarity in heme interactions. Spectrophotometric analysis disclosed that the characteristic shift in the Soret peak for hemoglobin produced by NO was also produced by an endothelium-derived factor released from washed aortic endothelial cells by acetylcholine or A23187. Pyrogallol, via the action of superoxide anion, markedly inhibited the spectral shifts, relaxant effects, and cGMP accumulating actions produced by both EDRF and NO. Superoxide dismutase enhanced the relaxant and cGMP accumulating effects of both EDRF and NO. Thus, EDRF and NO are inactivated by superoxide in a closely similar manner. We conclude, therefore, that EDRF from artery and vein is either NO or a chemically related radical species.
本研究的目的是阐明内皮源性舒张因子（EDRF）与一氧化氮自由基（NO）在性质上的密切相似性。只要有可能，还对动脉和静脉的EDRF进行了比较。在血管舒张实验中，分别使用乙酰胆碱和缓激肽作为牛肺内动脉和静脉分离环的内皮依赖性舒张剂，并用NO舒张去内皮环。氧合血红蛋白对内皮依赖性舒张和NO诱导的舒张产生几乎相同的浓度依赖性抑制作用。氧合血红蛋白和氧合肌红蛋白降低了环磷酸鸟苷（cGMP）水平，增加了未摩擦的动脉和静脉的张力，并消除了由内皮依赖性舒张剂和NO引起的血管cGMP的显著积累。一氧化碳消除或逆转了氧合血红蛋白对动脉和静脉舒张反应及cGMP积累的显著抑制作用及其收缩作用。这些观察结果表明，EDRF和NO在与氧合血红蛋白的相互作用中具有相同的性质。动脉和静脉的EDRF以及NO均通过血红素依赖性机制激活纯化的可溶性鸟苷酸环化酶，从而揭示了血红素相互作用中的另一个相似之处。分光光度分析表明，NO产生的血红蛋白Soret峰的特征性位移也由乙酰胆碱或A23187从洗涤过的主动脉内皮细胞释放的内皮源性因子产生。焦性没食子酸通过超氧阴离子的作用，显著抑制了EDRF和NO产生的光谱位移、舒张作用和cGMP积累作用。超氧化物歧化酶增强了EDRF和NO的舒张作用和cGMP积累作用。因此，EDRF和NO以非常相似的方式被超氧化物灭活。因此，我们得出结论，动脉和静脉的EDRF要么是NO，要么是化学相关的自由基物种。
