CORRECTION OF ENDOTHELIAL DYSFUNCTION IN CORONARY MICROCIRCULATION OF HYPERCHOLESTEROLEMIC PATIENTS BY L-ARGININE
CORRECTION OF ENDOTHELIAL DYSFUNCTION IN CORONARY MICROCIRCULATION OF HYPERCHOLESTEROLEMIC PATIENTS BY L-ARGININE
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DOI：
10.1016/0140-6736(91)92372-9
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发表时间：
1991-12-21
期刊：
影响因子：
168.9
通讯作者：
JUST, H
中科院分区：
文献类型：
--
作者：
DREXLER, H;ZEIHER, AM;JUST, H
高胆固醇血症损害内皮功能，可能是通过干扰内皮源性松弛因子由其前体l -精氨酸在细胞内形成。因此研究了l -精氨酸是否能逆转高胆固醇血症引起的冠状动脉循环内皮功能障碍。测定8例高胆固醇血症患者（平均血清胆固醇7.8 [SE 0.3] mmol/l）和7例年龄相匹配的对照组在冠状动脉内灌注内皮依赖性药物乙酰胆碱（0.036、0.36、3.6 mu-g/min）前后心外膜动脉横截面面积和冠状动脉血流速度。然后检查冠状动脉内输注l -精氨酸（160 μ mol/min）对这些测量的影响。在对照组中，乙酰胆碱诱导左前降支心外膜动脉段中度剂量依赖性收缩，并增加冠状动脉血流量（最高剂量时增加239% [SE 57]）。在高胆固醇血症患者中，乙酰胆碱对心外膜段的血管收缩作用与对照组相似，但乙酰胆碱对冠状动脉血流量的增加明显减弱（最高剂量：61%[19]，与对照组相比p < 0.02）。l -精氨酸恢复了乙酰胆碱引起的高胆固醇血症患者血流量的增加（与基线相比为198%[61]），但对对照组的冠状动脉血流量没有影响。研究结果表明，高胆固醇血症损害冠状动脉微循环的内皮依赖性扩张，这种损害可以通过短期服用l -精氨酸来恢复。l -精氨酸可能成为治疗高胆固醇血症引起的冠状动脉内皮异常的基础的可能性值得研究。
Hypercholesterolaemia impairs endothelial function, possibly by interference with the intracellular formation of endothelium-derived relaxing factor from its precursor L-arginine. Whether L-arginine reverses hypercholesterolaemia-induced endothelial dysfunction in the coronary circulation was thus investigated.Epicardial artery cross-sectional area and coronary blood flow velocity were measured in 8 hypercholesterolaemic patients (mean serum cholesterol 7.8 [SE 0.3] mmol/l) and 7 age-matched controls before and after graded intracoronary infusions of the endothelium-dependent agent acetylcholine (0.036, 0.36, 3.6-mu-g/min). The effect of intracoronary infusion of L-arginine (160-mu-mol/min via the guiding catheter) on these measurements was then examined. In controls, acetylcholine induced a moderate dose-dependent constriction of the epicardial artery segment of the left anterior descending artery and increased coronary blood flow (by 239% [SE 57] at the highest dose). In patients with hypercholesterolaemia, the vasoconstrictive effect of acetylcholine on epicardial segments was similar to that in controls, but the increase in coronary blood flow with acetylcholine was significantly attenuated (highest dose: 61% [19), p < 0.02 vs controls). L-arginine restored the acetylcholine-induced increase in blood flow in patients with hypercholesterolaemia (198% [61] vs baseline) but did not affect coronary blood flow in controls.The findings suggest that hypercholesterolaemia impairs endothelium-dependent dilatation of the coronary microcirculation and that this impairment can be restored by short-term administration of L-arginine. The possibility that L-arginine might form the basis of treatment for coronary endothelial abnormalities induced by hypercholesterolaemia could be worth investigating.