Zeiher A M, Drexler H, Saurbier B, Just H
Department of Cardiology, University of Freiburg, Germany.
J Clin Invest. 1993 Aug;92(2):652-62. doi: 10.1172/JCI116634.
The effects of age, atherosclerosis, hypertension, and hypercholesterolemia on vascular function of the coronary circulation were studied by subselective intracoronary infusions of acetylcholine, which releases endothelium-derived relaxing factor, and papaverine, which directly relaxes vascular smooth muscle, in normal patients (n = 18; no risk factors for coronary artery disease), in patients with evidence of early atherosclerosis but normal cholesterol levels and normal blood pressure (n = 12), in patients with hypertension without left ventricular hypertrophy (n = 12), and in patients with hypercholesterolemia (n = 20). Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia. The capacity of the coronary system to increase blood flow in response to acetylcholine was similar in normal and normocholesterolemic patients with epicardial atherosclerosis and/or hypertension but was significantly impaired in patients with hypercholesterolemia, irrespective of evidence of epicardial atherosclerotic lesions. Age (r = -0.62, P < 0.0001) and total serum cholesterol levels (r = -0.70; P < 0.0001) were the only significant independent predictors of a blunted coronary blood flow response to acetylcholine. Thus, hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension.
通过对正常患者（n = 18；无冠状动脉疾病危险因素）、有早期动脉粥样硬化证据但胆固醇水平正常且血压正常的患者（n = 12）、无左心室肥厚的高血压患者（n = 12）以及高胆固醇血症患者（n = 20）进行选择性冠状动脉内输注乙酰胆碱（释放内皮源性舒张因子）和罂粟碱（直接舒张血管平滑肌），研究年龄、动脉粥样硬化、高血压和高胆固醇血症对冠状动脉循环血管功能的影响。罂粟碱诱导的冠状动脉血流最大增加在正常组中显著更大，但早期动脉粥样硬化患者组、高血压患者组和高胆固醇血症患者组之间未观察到差异。正常和胆固醇水平正常且有冠状动脉粥样硬化和/或高血压的患者对乙酰胆碱反应时冠状动脉系统增加血流的能力相似，但高胆固醇血症患者的这种能力显著受损，无论有无冠状动脉粥样硬化病变的证据。年龄（r = -0.62，P < 0.0001）和血清总胆固醇水平（r = -0.70；P < 0.0001）是冠状动脉血流对乙酰胆碱反应减弱的仅有的显著独立预测因素。因此，高胆固醇血症和高龄选择性地损害冠状动脉微血管对乙酰胆碱的内皮介导舒张，而在年龄匹配、胆固醇水平正常且有冠状动脉粥样硬化和/或高血压证据的患者中，内皮功能障碍仅限于心外膜动脉。
