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L-arginine supplementation in hypercholesterolemic rabbits normalizes leukocyte adhesion to non-endothelial matrix.

机译:高胆固醇血症兔子的L-精氨酸补充可以使白细胞与非内皮基质的粘附正常化。

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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%). CONCLUSION: 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.
机译:L-精氨酸减缓动脉粥样硬化病变的发展,改善内皮依赖性舒张,并减少高胆固醇血症兔的血管超氧阴离子产生。这些有益的作用归因于内皮层内一氧化氮的L-精氨酸依赖性形成。然而,尚未研究L-精氨酸对其他细胞的直接作用。我们假设在高胆固醇血症中,L-精氨酸还通过对白细胞的直接抑制作用而特异性发挥作用,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(洛伐他汀)进行了比较,已知后者可以减弱动脉粥样硬化的进展。给兔子饲喂富含胆固醇的饮食,从第五周起开始服用洛伐他汀(10毫克/天),维生素E(300毫克/天)或L-精氨酸(饮用水中2%)。 16周后,测定血液胆固醇浓度并测量白细胞对棉绒的粘附。为了排除任何内皮介导的作用,避免了对内皮细胞的粘附测定。富含胆固醇的饮食可增加血浆胆固醇浓度(19 +/- 3比1427 +/- 117 mg / dl)。胆固醇水平不受L-精氨酸(1344 +/- 163 mg / dl)或维生素E(1312 +/- 243 mg / dl)的影响。与胆固醇组相比,洛伐他汀治疗可将胆固醇浓度降低35%(899 +/- 51,相对于胆固醇,p <0.05)。胆固醇饮食显着增加了白细胞对棉绒的附着力(16 +/- 3%对27 +/- 4%,p <0.05)。洛伐他汀或维生素E对白细胞黏附没有影响(31 +/- 4%,39 +/- 5),而L-精氨酸完全使黏附正常化(8.8 +/- 3%)。结论:饲喂高胆固醇饮食的兔子白细胞粘附增加,不受洛伐他汀或维生素E治疗的影响,但通过补充L-精氨酸可预防。 L-精氨酸对白细胞粘附的直接抑制作用可能有助于使用该物质观察到的有益作用。

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