[Therapeutic options for improvement of myocardial perfusion in coronary atherosclerosis].

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.