Brandes R P, Brandes S, Böger R H, Bode-Böger S M, Mügge A
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany.
Life Sci. 2000;66(16):1519-24. doi: 10.1016/s0024-3205(00)00469-0.
L-arginine slows the development of atheromatous lesions, improves endothelium-dependent relaxation, and reduces the vascular superoxide anion production in hypercholesterolemic rabbits. These beneficial effects have been attributed to L-arginine-dependent formation of nitric oxide within the endothelial layer; a direct effect of L-arginine on other cells, however, has not been investigated. We hypothesised that in hypercholesterolemia L-arginine also specifically acts via a direct inhibitory effect on leukocytes, without affecting endothelial cells. The action of L-arginine was compared to vitamin E and the HMG CoA reductase inhibitor lovastatin which are known to attenuate progression of atherosclerosis. Rabbits were fed cholesterol enriched diet and from week five on lovastatin (10 mg/day), vitamin E (300 mg/d) or L-arginine (2% in drinking water) were given. After 16 weeks, blood cholesterol concentration was determined and leukocyte adhesion to cotton wool was measured. In order to exclude any endothelium-mediated effects an adhesion assay to endothelial cells was avoided. Cholesterol-enriched diet increased plasma cholesterol concentration (19+/-3 vs. 1427+/-117 mg/dl). Cholesterol levels were not affected by L-arginine (1344+/-163 mg/dl) or vitamine E (1312+/-243 mg/dl). Lovastatin treatment reduced cholesterol concentration by 35% as compared to the cholesterol group (899+/-51, p<0.05 vs. cholesterol). Cholesterol diet significantly increased leukocyte adhesion to cotton wool (16+/-3% vs 27+/-4%, p<0.05). Lovastatin or vitamine E had no effect on leukocyte adhesion (31+/-4%, 39+/-5), whereas L-arginine completely normalized adhesion (8.8+/-3%).
Rabbits fed high cholesterol diet have increased leukocyte adhesion, which is not affected by lovastatin or vitamine E treatment, but prevented by L-arginine supplementation. A direct inhibitory effect of L-arginine on leukocyte adhesion may contribute to the beneficial effects observed with this substance.
L-精氨酸可减缓动脉粥样硬化病变的发展，改善内皮依赖性舒张功能，并减少高胆固醇血症兔子体内血管超氧阴离子的产生。这些有益作用归因于在内皮层中依赖L-精氨酸生成一氧化氮；然而，L-精氨酸对其他细胞的直接作用尚未得到研究。我们推测，在高胆固醇血症中，L-精氨酸还通过对白细胞的直接抑制作用发挥特异性作用，而不影响内皮细胞。将L-精氨酸的作用与维生素E和HMG CoA还原酶抑制剂洛伐他汀进行比较，已知这两种物质可减缓动脉粥样硬化的进展。给兔子喂食富含胆固醇的饮食，从第五周开始给予洛伐他汀（10毫克/天）、维生素E（300毫克/天）或L-精氨酸（饮用水中含2%）。16周后，测定血液胆固醇浓度，并测量白细胞对棉絮的黏附情况。为了排除任何内皮介导的影响，避免进行对内皮细胞的黏附试验。富含胆固醇的饮食会增加血浆胆固醇浓度（19±3对1427±117毫克/分升）。胆固醇水平不受L-精氨酸（1344±163毫克/分升）或维生素E（1312±243毫克/分升）的影响。与胆固醇组相比，洛伐他汀治疗可使胆固醇浓度降低35%（899±51，与胆固醇组相比p<0.05）。胆固醇饮食显著增加白细胞对棉絮的黏附（16±3%对27±4%，p<0.05）。洛伐他汀或维生素E对白细胞黏附无影响（31±4%，39±5%），而L-精氨酸可使黏附完全恢复正常（8.8±3%）。
喂食高胆固醇饮食的兔子白细胞黏附增加，洛伐他汀或维生素E治疗对此无影响，但补充L-精氨酸可预防。L-精氨酸对白细胞黏附的直接抑制作用可能有助于观察到该物质的有益效果。
