ENDOTHELIUM-DERIVED RELAXING FACTOR PRODUCED AND RELEASED FROM ARTERY AND VEIN IS NITRIC-OXIDE

ENDOTHELIUM-DERIVED RELAXING FACTOR PRODUCED AND RELEASED FROM ARTERY AND VEIN IS NITRIC-OXIDE
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DOI:
10.1073/pnas.84.24.9265
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发表时间:
1987-12-01
影响因子:
11.1
通讯作者:
CHAUDHURI, G
CHAUDHURI, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
IGNARRO, LJ;BUGA, GM;CHAUDHURI, G

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本研究的目的是确定一氧化氮(NO)是否负责内皮源性舒张因子(EDRF)引起的血管平滑肌舒张。EDRF是从动脉和静脉释放的不稳定体液物质,介导内皮依赖性血管舒张剂的作用。NO是一种不稳定的非内皮依赖性血管扩张剂,从血管扩张药物如硝普钠和硝酸甘油酯中释放。我们多次观察到NO对血管平滑肌的作用与EDRF的作用非常相似。在本研究中,从灌注牛肺内动脉和静脉释放的EDRF的血管效应与通过在级联排列的内皮剥脱的动脉和静脉条上灌注递送的NO的效应进行了比较。EDRF与NO没有区别,因为两者都是不稳定的(t1/2 = 3-5秒),被邻苯三酚或超氧阴离子灭活,被超氧化物歧化酶稳定,并被氧合血红蛋白或钾抑制。EDRF和NO都产生了动脉和静脉中环GMP积累的可比增加,并且这种环GMP积累被邻苯三酚、氧合血红蛋白、钾和亚甲蓝抑制。EDRF的化学鉴定为NO,或一个不稳定的亚硝基物种,通过两个程序。首先,像NO一样,从新鲜分离的主动脉内皮细胞释放的EDRF与血红蛋白反应产生亚硝基血红蛋白。其次,EDRF和NO各自类似地促进对氨基苯磺酸的重氮化,并且在与N-(1-萘基)-乙二胺偶联后产生相同的反应产物。因此,从动脉和静脉释放的EDRF具有与NO相同的生物学和化学性质。
The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is an unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. We have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were compared with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile (t1/2 = 3-5 sec), inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. First, like NO, EDRF released from freshly isolated aortic endothelial cells reacted with hemoglobin to yield nitrosylhemoglobin. Second, EDRF and NO each similarly promoted the diazotization of sulfanilic acid and yielded the same reaction product after coupling with N-(1-naphthyl)-ethylenediamine. Thus, EDRF released from artery and vein possess identical biological and chemical properties as NO.