Bassenge E, Stewart D J
Department of Applied Physiology, University of Freiburg, West Germany.
Cardiovasc Drugs Ther. 1988 May;2(1):27-34. doi: 10.1007/BF00054249.
Recent advances in the understanding of vascular physiology have furnished new aspects in the treatment of angina pectoris by various vasodilators. Upon stimulation by various factors (viscous drag from increased flow, pulsatile stretch, ADP/ATP, norepinephrine, serotonin), the coronary endothelium releases a vasodilator called endothelium-derived relaxant factor (EDRF). This factor has recently been shown to probably be nitric oxide (NO), which is identical to the active compound of nitroglycerin. EDRF (NO) dilates both large epicardial arteries and also coronary resistance vessels. It also has a strong platelet antiaggregant effect. The predominant effect of Ca2+ antagonists is on resistance vessels, increasing myocardial perfusion and viscous drag acting upon the endothelial lining. This, in turn, stimulates EDRF (NO) release in epicardial arteries and dilation. This additional nitrate-like effect augments the direct vasodilator effect of Ca2+ antagonists. Lack of normal endothelial function results in diminished capacity to dilate, and sometimes even in a shift from dilator to constrictor effects, paralleled by an increased tendency for platelet adhesion, activation, and thrombosis, which is still enhanced when plasma low density lipoprotein (LDL) is augmented. EDRF release, vasodilator capacity, and antiaggregant effects are reduced when LDL is high. Nitrates have a direct, endothelium-independent dilator effect, particularly on large coronary arteries, which seems even more pronounced when the endothelium is absent, but only when the vessel segment is still compliant. Therefore nitrates may particularly be effective in vessels with deficient EDRF release.
在血管生理学认识方面的最新进展为各种血管扩张剂治疗心绞痛提供了新的思路。在受到各种因素（血流增加产生的粘性阻力、搏动性牵张、二磷酸腺苷/三磷酸腺苷、去甲肾上腺素、5-羟色胺）刺激时，冠状动脉内皮会释放一种名为内皮源性舒张因子（EDRF）的血管扩张剂。最近研究表明，这种因子可能就是一氧化氮（NO），它与硝酸甘油的活性成分相同。EDRF（NO）可使心外膜大血管和冠状动脉阻力血管都发生扩张。它还具有很强的抗血小板聚集作用。钙离子拮抗剂的主要作用靶点是阻力血管，可增加心肌灌注以及作用于内皮的粘性阻力。这反过来又刺激心外膜动脉释放EDRF（NO）并使其扩张。这种额外的类硝酸盐效应增强了钙离子拮抗剂的直接血管扩张作用。内皮功能异常会导致血管扩张能力下降，有时甚至会出现从扩张作用向收缩作用的转变，同时血小板黏附、活化和血栓形成的倾向增加，当血浆低密度脂蛋白（LDL）升高时这种倾向会进一步增强。LDL水平升高时，EDRF释放、血管扩张能力和抗聚集作用都会降低。硝酸盐具有直接的、不依赖内皮的扩张作用，尤其对大冠状动脉，当内皮缺失时这种作用似乎更明显，但前提是血管段仍具有顺应性。因此，硝酸盐可能对EDRF释放不足的血管特别有效。
