Zeiher A M, Schächlinger V, Hohnloser S H, Saurbier B, Just H
Department of Internal Medicine III, Universitätsklinik Freiburg, Germany.
Circulation. 1994 Jun;89(6):2525-32. doi: 10.1161/01.cir.89.6.2525.
Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with deficient endothelium-mediated dilation and thereby contribute to the abnormal reactivity of atherosclerotic arteries in vivo.
In 26 patients without focal stenoses in the left anterior descending coronary artery, acetylcholine (0.036 to 3.6 micrograms/mL) was infused into the artery to evaluate endothelium-mediated vasodilation. Segmental vasomotor responses to acetylcholine were correlated with the local extent of atherosclerotic wall thickening quantitated by intracoronary ultrasound examination. Seventeen of the patients also underwent cold pressor testing to assess the vasoreactivity to sympathetic activation. The response of coronary artery segments to acetylcholine varied from 35% dilation to 52% constriction and demonstrated a segmental pattern, with dilation and constriction observed in different segments of the same artery. The vasomotor response to acetylcholine was closely correlated with the extent of local atherosclerotic wall thickening (r = -.82, P < .0001). Over the entire range of atherosclerotic wall thickening, segments from patients with elevated high-density lipoprotein (HDL) cholesterol serum levels (> 75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P < .01 at the maximal acetylcholine concentration) compared with segments from patients with HDL cholesterol < 75th percentile. The degree of constriction or dilation in response to the acetylcholine infusion correlated with the response to cold pressor testing (r = .75, P < .0001). Again, the cold pressor test-induced constrictor response was significantly (P < .05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patients with HDL cholesterol < 75th percentile despite equal degrees of atherosclerotic wall thickening.
Coronary vasomotor responses to the endothelium-dependent dilator acetylcholine and to sympathetic stimulation by cold pressor test correlate with local atherosclerotic wall thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic "plaque load" in human epicardial arteries in vivo. Elevated HDL cholesterol serum levels ameliorate abnormal vasoconstriction at any given extent of atherosclerotic wall thickening, suggesting that HDL cholesterol exerts a beneficial effect on abnormal vascular reactivity, a fundamental functional disturbance associated with coronary atherosclerosis.
随着动脉粥样硬化的发展，血管反应性异常代表了血管生物学的一种基本紊乱。由于内皮舒张功能在控制血管运动张力中起关键作用，我们推测动脉粥样硬化壁增厚可能直接干扰内皮介导的舒张功能不足，从而导致体内动脉粥样硬化动脉的反应性异常。
在26例左前降支冠状动脉无局灶性狭窄的患者中，向动脉内注入乙酰胆碱（0.036至3.6微克/毫升）以评估内皮介导的血管舒张。对乙酰胆碱的节段性血管运动反应与通过冠状动脉内超声检查定量的动脉粥样硬化壁增厚的局部范围相关。17例患者还接受了冷加压试验以评估对交感神经激活的血管反应性。冠状动脉节段对乙酰胆碱的反应从35%扩张到52%收缩不等，并呈现节段性模式，在同一动脉的不同节段观察到扩张和收缩。对乙酰胆碱的血管运动反应与局部动脉粥样硬化壁增厚的程度密切相关（r = -0.82，P < 0.0001）。在整个动脉粥样硬化壁增厚范围内，高密度脂蛋白（HDL）胆固醇血清水平升高（>第75百分位数）的患者的节段与HDL胆固醇<第75百分位数的患者的节段相比，对乙酰胆碱的收缩反应明显减弱（在最大乙酰胆碱浓度下P < 0.01）。对乙酰胆碱输注的收缩或扩张程度与对冷加压试验的反应相关（r = 0.75，P < 0.0001）。同样，尽管动脉粥样硬化壁增厚程度相同，但HDL胆固醇血清水平升高的患者的节段与HDL胆固醇<第75百分位数的患者的节段相比，冷加压试验诱导的收缩反应明显减弱（P < 0.05）。
冠状动脉对内皮依赖性舒张剂乙酰胆碱的血管运动反应以及对冷加压试验交感神经刺激的反应与局部动脉粥样硬化壁增厚相关。因此，局部血管反应性异常的程度与体内人类心外膜动脉中动脉粥样硬化“斑块负荷”的程度密切相关。在任何给定的动脉粥样硬化壁增厚程度下，HDL胆固醇血清水平升高可改善异常血管收缩，表明HDL胆固醇对异常血管反应性具有有益作用，异常血管反应性是与冠状动脉粥样硬化相关的一种基本功能紊乱。
