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

Applied Physiology Research Center and Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. .
Nutrition & Metabolism (Impact Factor: 3.26). 02/2009; 6(1):13. DOI: 10.1186/1743-7075-6-13
Source: PubMed


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.

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    • "It has been suggested that reduced bioavailability of NO by insulin resistance may be an additional pathogenic factor in atherosclerosis [7,8]. The exact molecular relationship between insulin, ED and atherosclerosis is presently unknown [9]. In order to elucidate this relationship, studying the early variation of insulin during induction of hypercholesterolemia may help cognizance the pathogenesis of atherosclerosis. "
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