Schächinger V
Medizinische Klinik IV, Abteilung Kardiologie, Johann-Wolfgang-Goethe-Universität Frankfurt.
Herz. 1998 Mar;23(2):116-29. doi: 10.1007/BF03044542.
The combination of morphological atherosclerotic alterations of coronary vessels and disturbance of coronary vasomotor control of epicardial and resistance vessels determines the amount of myocardial oxygen supply. The endothelium plays a crucial role for functional alterations of the coronary vessels in patients with early atherosclerosis or risk factors for coronary artery disease. A therapy which aims to ameliorate endothelium-dependent vasodilator capacity improves myocardial perfusion in patients with coronary artery disease. Thereby, even in patients with angiographically normal or minimally diseased coronary vessels who develop myocardial ischemia due to microvascular disease, symptomatic improvement might be achieved. Control of coronary vasomotor tone and proliferation processes within the vessel wall are both determined by the redox equilibrium of nitric oxide (NO) and superoxide radicals (O2-), induced by angiotensin II. Thus, vasomotor control and vessel wall proliferation is closely related to each other. Aim of a therapeutic intervention to enhance NO bioactivity is either to increase NO production in the endothelium or to decrease O2- production, which rapidly inactivates NO. NO bioactivity can be ameliorated by ACE-inhibitors, increase of shear stress on the endothelium by physical exercise, estrogens or L-arginine. For these therapies clinically an improvement of endothelial vasodilator function could be shown. In addition, improvement of endothelial vasodilator function can be achieved by a treatment which reduced oxidative stress in the vascular wall such as antioxidants and, especially, lipid lowering drugs. Endothelin-antagonists and angiotensin II receptor-blockers are promising to improve endothelial dysfunction. However, these therapies have to be validated. Most therapy strategies, which have shown to ameliorate endothelial dysfunction, are also able to improve prognosis of the patients. Whether endothelial dysfunction alone--without evidence of overt coronary atherosclerosis--is sufficient to justify a long-term therapy to improve prognosis, still has to be clarified.
冠状动脉的形态学动脉粥样硬化改变与心外膜血管及阻力血管的冠状动脉血管舒缩控制紊乱相结合，决定了心肌的供氧量。内皮对于早期动脉粥样硬化患者或冠心病危险因素患者冠状动脉的功能改变起着关键作用。旨在改善内皮依赖性血管舒张能力的治疗可改善冠心病患者的心肌灌注。因此，即使在冠状动脉造影正常或病变轻微但因微血管疾病而发生心肌缺血的患者中，也可能实现症状改善。血管紧张素II诱导的一氧化氮（NO）和超氧阴离子自由基（O2-）的氧化还原平衡决定了冠状动脉血管舒缩张力的控制和血管壁内的增殖过程。因此，血管舒缩控制与血管壁增殖密切相关。增强NO生物活性的治疗干预目标要么是增加内皮中NO的生成，要么是减少迅速使NO失活的O2-生成。ACE抑制剂、体育锻炼、雌激素或L-精氨酸增加内皮上的剪切应力可改善NO生物活性。临床上已证实这些治疗可改善内皮舒张功能。此外，通过减少血管壁氧化应激的治疗，如抗氧化剂，尤其是降脂药物，也可实现内皮舒张功能的改善。内皮素拮抗剂和血管紧张素II受体阻滞剂有望改善内皮功能障碍。然而，这些治疗方法必须经过验证。大多数已证明可改善内皮功能障碍的治疗策略也能够改善患者预后。仅内皮功能障碍（无明显冠状动脉粥样硬化证据）是否足以证明进行长期治疗以改善预后，仍有待阐明。
