Tschudi M R, Lüscher T F
Department Medizin, Inselspital Bern/Schweiz.
Herz. 1996 Jun;21 Suppl 1:50-60.
The endothelium takes part in the regulation of vascular tone through the production of endothelium-derived relaxing and contracting factors. The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). The NO molecule has one unpaired electron and readily reacts with oxygen, superoxide radicals, or transition metals. Therefore the measurement of the concentration of NO in biological systems is a challenging analytical problem. NO is formed from L-arginine via constitutive NO synthase. It is released under basal conditions and in response to mechanical stimuli such as shear stress and in response to receptor-operated agonists such as bradykinin, serotonin, ADP/ATP, thrombin, histamine and substance P. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cyclic GMP) and to relaxation. In addition to its effect on vascular smooth muscle, NO is also released albuminally to interact with circulating platelets. Increases in cyclic GMP in platelets are associated with a decreased adhesion and aggregation. In endothelial cells, NO inhibits its own production as well as that of the vasoconstrictor peptide endothelin-1. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Under certain conditions such as inflammation, NO may also be formed via inducible nitric oxide synthase by smooth muscle cells, endothelium and monocytes. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries in which the release of NO is inhibited or impaired or in the absence of the endothelium. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties. Nitrates can at least in part substitute the endogenous nitrovasodilator in disease states with impaired formation of NO.
内皮细胞通过产生内皮衍生的舒张和收缩因子参与血管张力的调节。血管壁内皮细胞内的L-精氨酸途径是内源性血管舒张剂一氧化氮（NO）的产生来源。NO分子有一个未成对电子，容易与氧、超氧自由基或过渡金属发生反应。因此，在生物系统中测量NO的浓度是一个具有挑战性的分析问题。NO由L-精氨酸通过组成型一氧化氮合酶形成。它在基础条件下释放，并对机械刺激如剪切应力作出反应，以及对受体介导的激动剂如缓激肽、5-羟色胺、ADP/ATP、凝血酶、组胺和P物质作出反应。NO是循环中内皮依赖性舒张的介质，通过激活血管平滑肌中的可溶性鸟苷酸环化酶发挥作用，进而导致环磷酸鸟苷（cGMP）的形成并引起舒张。除了对血管平滑肌的作用外，NO还通过白蛋白释放与循环中的血小板相互作用。血小板中cGMP的增加与粘附和聚集的减少有关。在内皮细胞中，NO抑制其自身以及血管收缩肽内皮素-1的产生。因此，内皮衍生的NO通过其血管舒张和抗聚集特性，防止循环中的血管痉挛和血栓形成，从而有助于维持向心脏等重要器官的血流。在某些条件下，如炎症，平滑肌细胞、内皮细胞和单核细胞也可通过诱导型一氧化氮合酶形成NO。治疗性硝酸盐也通过从其分子中释放NO并激活可溶性鸟苷酸环化酶发挥作用。它们的作用在NO释放受到抑制或受损的动脉或无内皮的动脉中尤为明显。因此，内皮L-精氨酸途径在局部血流调节中通过其血管舒张和抗血小板特性发挥重要的保护作用。在NO形成受损的疾病状态下，硝酸盐至少可以部分替代内源性血管舒张剂。
