Applied Physiology Research Center and Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Nutr Metab (Lond). 2009 Mar 24;6:13. doi: 10.1186/1743-7075-6-13.
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.
内皮功能障碍（ED）是心血管事件的独立预测因子。ED 也是一种可逆转的紊乱，而像 L-精氨酸这样的一氧化氮供体可能会促进这一过程。尽管多项研究取得了积极的结果，但也有一些研究表明，L-精氨酸给药并没有改善患者的内皮依赖性扩张或炎症状态。在这项研究中，我们考虑了在高胆固醇血症兔中 L-精氨酸对冠状动脉脂肪条纹形成和 ED 生物标志物的早期和晚期影响。
36 只雄性白色兔子被随机分为 3 组。兔子喂食 1%高胆固醇饮食（LP 组，n = 15），或高胆固醇饮食加口服 L-精氨酸（3%在饮用水中）（EP 组，n = 15）或标准饮食（对照组，n = 6）4 周（第 I 阶段）。之后，所有动物均喂食正常饮食 4 周（第 II 阶段）。在第 2 阶段，停止 EP 组的 L-精氨酸给药，并开始 LP 组的 L-精氨酸给药。在实验前和第 4、8 周后比较各组的血浆脂质、血管性血友病因子（vWF）和亚硝酸盐水平。在实验的第 4 和第 8 周后测量冠状动脉脂肪条纹形成。
第 I 阶段后，LP 和 EP 两组的血浆脂质水平均显著升高。高胆固醇血症导致 LP 组 vWF 释放显著增加。EP 组的 L-精氨酸补充导致血浆亚硝酸盐显著增加。LP 组的 vWF 高于其他组（p < 0.05）。在第 II 阶段结束时，尽管 LP 组开始补充 L-精氨酸，EP 组停止 L-精氨酸给药，但 LP 组冠状动脉的脂肪条纹病变明显多于 EP 组。此外，L-精氨酸补充并未导致 LP 组亚硝酸盐水平显著增加。
早期通过 L-精氨酸进行预防可能有助于预防 ED，但我们的研究并未提示进行治疗。在不可逆血管损伤发生之前，考虑 ED-除了控制心血管危险因素之外，在动脉粥样硬化及其临床结果的一级预防中具有合理性。
