The discovery of nitric oxide and its role in vascular biology
The discovery of nitric oxide and its role in vascular biology
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DOI：
10.1038/sj.bjp.0706458
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发表时间：
2006-01-01
影响因子：
7.3
通讯作者：
Higgs, EA
中科院分区：
文献类型：
--
作者：
Moncada, S;Higgs, EA
一氧化氮（NO）是药理学的一个相对较新的领域，因为开创该领域的论文仅在25年前发表。然而，它的影响是这样的，迄今为止，已经发表了31000多篇论文，标题中没有，65,000多篇以某种方式提到它。NO与内皮源性舒张因子的鉴定及其从L-精氨酸合成的发现导致认识到L-精氨酸：NO途径是广泛的并且起着多种生理作用。这些包括维持血管张力，中枢和外周神经系统的神经递质功能，以及介导细胞防御。此外，NO与线粒体系统相互作用以调节细胞呼吸并增加活性氧的产生，从而触发细胞存活或死亡的机制。本文综述了NO在心血管系统中的作用，除了维持血管舒张张力外，它还抑制血小板聚集和粘附，调节平滑肌细胞增殖。NO在许多心血管疾病中起着重要作用，几乎每一个危险因素都与内皮细胞NO生成减少有关。基础NO合成或作用减少导致血管收缩、血压升高和血栓形成。相反，NO的过量产生导致血管舒张、低血压、血管渗漏和细胞代谢的破坏。NO生成的适当药理学或分子生物学操作无疑将证明在这种情况下是有益的。
Nitric oxide (NO) is a relative newcomer to pharmacology, as the paper which initiated the Field was published only 25 years ago. Nevertheless its impact is such that to date more than 3 1,000 papers have been published with NO in the title and more than 65,000 refer to it in some way. The identification of NO with endothelium-derived relaxing factor and the discovery of its synthesis from L-arginine led to the realisation that the L-arginine: NO pathway is widespread and plays a variety or physiological roles. These include the maintenance of vascular tone, neurotransmitter function in both the central and peripheral nervous systems, and mediation of cellular defence. In addition, NO interacts with mitochondrial systems to regulate Cell respiration and to augment the generation of reactive oxygen species, thus triggering mechanisms of cell survival or death. This review will focus on the role of NO in the cardiovascular system where, in addition to maintaining a vasodilator tone, it inhibits platelet aggregation and adhesion and modulates smooth muscle cell proliferation. NO has been iniplicated in a number of cardiovascular diseases and virtually every risk factor for these appears to be associated with a reduction in endothelial generation of NO. Reduced basal NO synthesis or action leads to vasoconstriction, elevated blood pressure and thrombus formation. By contrast, overproduction of NO leads to vasodilatation, hypotension, vascular leakage, and disruption of cell metabolism. Appropriate pharmacological or molecular biological manipulation of the generation of NO will doubtless prove beneficial in such conditions.