Kolodgie F D, Virmani R, Rice H E, Mergner W J
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.
Circ Res. 1990 Apr;66(4):1112-26. doi: 10.1161/01.res.66.4.1112.
The effects of varying degrees of atherosclerotic plaque on vascular responsiveness in aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits and New Zealand White (normal cholesterolemic) rabbits were studied. Ring segments from the aortic arch and thoracic aorta were mounted in organ chambers for isometric tension recording and measurement of endothelium-derived relaxing factor. WHHL rabbits were divided into three groups according to age: group 1, 3-5 months; group 2, 6-9 months; and group 3, 12-14 months. Atherosclerotic changes (expressed as a percent of total surface area) in the aortic arches in groups 1, 2, and 3 were 11 +/- 3% (mild), 28 +/- 6% (moderate), and 54 +/- 8% (severe) respectively; only occasional plaques were present in the thoracic aorta in all groups. Maximal contractions elicited with phenylephrine progressively decreased with increasing degrees of atherosclerotic plaque. Contractions evoked by histamine were augmented in all groups of WHHL rabbits when compared with controls, whereas those to serotonin were augmented only in vessels with mild atherosclerosis. As the severity of the intimal lesions increased, endothelium-dependent relaxations to acetylcholine, ATP, and calcium ionophore A23187 progressively decreased. Endothelium-independent relaxation to nitroglycerin was virtually complete in all segments. However, vessels with severe atherosclerosis were less sensitive to this agent as illustrated by a significant increase in the ED50 value. Scanning electron microscopy revealed a predominant loss of endothelial cells in the central regions of fibrous plaques. Thus, in WHHL rabbits, hypercholesterolemia and atherosclerosis result in an increased responsiveness of vascular smooth muscle to histamine and serotonin. Endothelium-mediated relaxation of vascular smooth muscle is reduced with the progression of atherosclerosis primarily due to a loss of endothelial cells.
研究了不同程度的动脉粥样硬化斑块对渡边遗传性高脂血症（WHHL）兔和新西兰白兔（正常胆固醇血症）主动脉血管反应性的影响。从主动脉弓和胸主动脉获取的血管环段被安装在器官浴槽中，用于等长张力记录和内皮衍生舒张因子的测量。WHHL兔根据年龄分为三组：第1组，3 - 5个月；第2组，6 - 9个月；第3组，12 - 14个月。第1、2和3组主动脉弓中的动脉粥样硬化变化（以总表面积的百分比表示）分别为11±3%（轻度）、28±6%（中度）和54±8%（重度）；所有组的胸主动脉中仅偶尔出现斑块。用去氧肾上腺素引起的最大收缩随着动脉粥样硬化斑块程度的增加而逐渐降低。与对照组相比，所有WHHL兔组中组胺引起的收缩均增强，而只有轻度动脉粥样硬化血管中5 - 羟色胺引起的收缩增强。随着内膜病变严重程度的增加，对乙酰胆碱、ATP和钙离子载体A23187的内皮依赖性舒张逐渐降低。对硝酸甘油的非内皮依赖性舒张在所有节段中几乎是完全的。然而，重度动脉粥样硬化血管对该药物的敏感性较低，表现为ED50值显著增加。扫描电子显微镜显示纤维斑块中央区域内皮细胞明显缺失。因此，在WHHL兔中，高胆固醇血症和动脉粥样硬化导致血管平滑肌对组胺和5 - 羟色胺的反应性增加。随着动脉粥样硬化的进展，内皮介导的血管平滑肌舒张减少，主要是由于内皮细胞的缺失。
