Wang B Y, Singer A H, Tsao P S, Drexler H, Kosek J, Cooke J P
Division of Cardiovascular Medicine, Stanford University School of Medicine, California 94305.
J Am Coll Cardiol. 1994 Feb;23(2):452-8. doi: 10.1016/0735-1097(94)90433-2.
This study was designed to test the hypothesis that long-term oral supplementation of dietary L-arginine (to provide a sustained elevation of nitric oxide activity) would inhibit atherogenesis in hypercholesterolemic rabbits, as assessed by histomorphometric measurements.
Endothelium-derived nitric oxide inhibits a number of processes that are critical in atherogenesis. Hypercholesterolemia reduces endothelial nitric oxide activity, and we postulate that this may promote atherogenesis. This reduction in nitric oxide activity can be reversed acutely by intravenous infusion of L-arginine, the precursor of nitric oxide. We show that dietary supplementation of L-arginine abrogates the development of coronary atheroma in hypercholesterolemic rabbits.
Male New Zealand White rabbits were fed normal rabbit chow, 1% cholesterol chow or 1% cholesterol chow with dietary arginine or methionine supplementation to increase their intake of these amino acids sixfold. After 1 or 10 weeks of dietary intervention, the left main and left anterior descending coronary arteries were harvested for histologic study. Plasma cholesterol measurements were elevated to the same degree in all groups of rabbits receiving the 1% cholesterol diet, whereas plasma arginine levels were doubled in the arginine-treated group. High density lipoprotein (HDL) cholesterol values were not affected by arginine treatment.
In rabbits receiving the 1% cholesterol diet, with or without methionine supplementation, light and electron microscopy revealed a marked increase from 1 to 10 weeks in the intimal accumulation of macrophages, associated with an increase in the intimal area of the left main coronary artery. By contrast, in arginine-treated hypercholesterolemic rabbits, there was a near absence of adherent monocytes and tissue macrophages and no progression of intimal thickness from 1 to 10 weeks.
Dietary supplements of L-arginine prevent intimal thickening in the coronary arteries of hypercholesterolemic rabbits. This antiatherogenic effect is not due to an alteration in plasma total cholesterol, HDL cholesterol or caloric or nitrogen balance. The data are consistent with the hypothesis that nitric oxide has antiatherogenic properties.
本研究旨在验证以下假设：通过组织形态计量学测量评估，长期口服补充膳食L-精氨酸（以持续提高一氧化氮活性）可抑制高胆固醇血症兔的动脉粥样硬化形成。
内皮源性一氧化氮可抑制动脉粥样硬化形成过程中的多个关键环节。高胆固醇血症会降低内皮一氧化氮活性，我们推测这可能会促进动脉粥样硬化形成。静脉输注一氧化氮的前体L-精氨酸可急性逆转这种一氧化氮活性的降低。我们发现，膳食补充L-精氨酸可消除高胆固醇血症兔冠状动脉粥样硬化的发展。
雄性新西兰白兔分别喂食正常兔粮、含1%胆固醇的兔粮或含1%胆固醇且补充膳食精氨酸或蛋氨酸的兔粮，以使这些氨基酸的摄入量增加至原来的六倍。经过1周或10周的饮食干预后，采集左主冠状动脉和左前降支冠状动脉进行组织学研究。所有接受1%胆固醇饮食的兔组血浆胆固醇测量值升高程度相同，而精氨酸治疗组的血浆精氨酸水平翻倍。高密度脂蛋白（HDL）胆固醇值不受精氨酸治疗的影响。
在接受1%胆固醇饮食的兔中，无论是否补充蛋氨酸，光镜和电镜检查均显示，从1周到10周，巨噬细胞在内膜的积聚显著增加，同时左主冠状动脉的内膜面积也增加。相比之下，在精氨酸治疗的高胆固醇血症兔中，几乎没有黏附的单核细胞和组织巨噬细胞，并且从1周到10周内膜厚度没有进展。
膳食补充L-精氨酸可预防高胆固醇血症兔冠状动脉内膜增厚。这种抗动脉粥样硬化作用并非由于血浆总胆固醇、HDL胆固醇或热量或氮平衡的改变。这些数据与一氧化氮具有抗动脉粥样硬化特性的假设一致。
