Early prevention by L-Arginine attenuates coronary atherosclerosis in a model of hypercholesterolemic animals; no positive results for treatment.

Early prevention by L-Arginine attenuates coronary atherosclerosis in a model of hypercholesterolemic animals; no positive results for treatment.
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DOI:
10.1186/1743-7075-6-13
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发表时间:
2009-03-24
影响因子:
4.5
通讯作者:
Sanei MH
Sanei MH
中科院分区:
医学3区
文献类型:
--
作者:
Javanmard SH;Nematbakhsh M;Sanei MH

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内皮功能障碍(艾德)是心血管事件的独立预测因子。艾德也是一种可逆性疾病,一氧化氮供体如L-精氨酸可能促进这一过程。尽管一些研究的结果是积极的,但也有一些研究表明,L-精氨酸给药不能改善患者的内皮依赖性舒张或炎症状态。在这项研究中,考虑了L-精氨酸对高胆固醇血症兔冠状动脉脂肪条纹形成和艾德生物标志物的早期和晚期影响。36只白色雄性家兔随机分为3组。实验第一阶段:实验动物分别喂饲1%高胆固醇饲料(LP组,n = 15)、高胆固醇饲料加口服3%精氨酸(EP组,n = 15)或标准饲料(对照组,n = 6)4周。之后,所有动物饲喂正常饮食4周(第II阶段)。第二阶段,EP组停用L-精氨酸,LP组开始使用L-精氨酸。比较实验前、后4周和8周血浆脂质、血管性血友病因子(vWF)和亚硝酸盐水平。在实验4周和8周后测量冠状动脉脂肪条纹形成。LP组和EP组血脂水平在第一阶段后均显著升高。高胆固醇血症可诱导LP组vWF释放明显增加。补充L-精氨酸导致EP组血浆亚硝酸盐水平显著升高。LP组vWF明显高于其他各组(p < 0.05)。II期结束时,尽管LP组开始补充L-精氨酸,EP组停用L-精氨酸,但LP组冠状动脉脂肪条纹病变明显多于EP组。此外,L-精氨酸补充并没有导致显着的亚硝酸盐的增量在LP组。早期应用L-精氨酸可能有助于预防艾德性勃起障碍,但本研究未提出治疗建议。在动脉粥样硬化的一级预防及其临床结局中,除了控制心血管危险因素外,在发生不可逆的血管损伤之前考虑ED似乎是合理的。
Endothelial dysfunction (ED) is an independent predictor of cardiovascular events. ED is also a reversible disorder, and nitric oxide donors like L-arginine may promote this process. Despite the positive results from several studies, there are some studies that have shown that L-arginine administration did not improve endothelium-dependent dilation or the inflammatory state of patients. In this study the early and the late effects of L-arginine on coronary fatty streak formation and ED biomarkers were considered in hypercholesterolemic rabbits. 36 white male rabbits randomly assigned in 3 groups. Rabbits were fed 1% high-cholesterol diet (LP group, n = 15), or high-cholesterol diet with oral L-arginine (3% in drinking water) (EP group, n = 15) or standard diet (control group, n = 6) for 4 weeks (phase I). Afterward, all animals were fed normal diet for 4 weeks (phase II). In the second phase, L-arginine was discontinued for EP group and was begun for LP group. The plasma levels of lipids, von Willebrand factor (vWF), and nitrite were compared before and after 4 and 8 weeks of experiment. Coronary fatty streak formation was measure after 4 and 8 weeks of experiment. The plasma levels of lipids were increased significantly in both groups of LP and EP after phase I. The hypercholesterolemia induced significant increased vWF release in LP group. The L-arginine supplementation led to significant plasma nitrite increment in EP group. The vWF in LP group was higher than other groups (p < 0.05). By the end of phase II, despite of start of L-arginine supplementation for LP group and L-arginine discontinuation in EP group, there were significantly more fatty streaks lesions in LP group coronary arteries than EP group. Furthermore, L-arginine supplementation did not result in significant nitrite increment in LP group. Early prevention by L-arginine may be helpful to prevent the ED, but our study did not suggest the treatment. It seems reasonable to consider ED-aside from control the cardiovascular risk factors in primary prevention of atherosclerosis and its clinical outcomes before development of irreversible vascular damage.
DOI: 10.1016/s0140-6736(96)07495-8
发表时间: 1997-05-17
期刊: LANCET
影响因子: 168.9
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通讯作者: Lopez, AD
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DOI: 10.1161/01.cir.96.4.1282
发表时间: 1997-08-19
期刊: CIRCULATION
影响因子: 37.8
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