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.

Download full-text


Available from: Shaghayegh Haghjooy Javanmard
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypercholesterolemia causes inflammation and insulin resistance in the vasculature. Previous data suggest that vascular endothelium is a physiological target of insulin. Dyslipidemia and atherosclerosis are disorders with endothelial dysfunction that are associated with an increased production of superoxide anion, and early deficit of nitric oxide (NO) production. We examined alteration of plasma levels of insulin, C-reactive protein (CRP) and total NO metabolites (NOx), as well as fatty streak formation in the rabbit model of hypercholesterolemia. White male rabbits were fed either a high-cholesterol diet (HC; 1% cholesterol, n = 6) or control diet (c, n = 6) for one month. The serum levels of Cholesterol, LDL, HDL, NOx, insulin and CRP were measured before and after study. By the end of study, rabbits' aorta was explored for fatty streak formation. The cholesterol-rich diet induced a significant increase in total cholesterol, LDL, and HDL as well as fatty streak lesions in HC group while there were no significant changes of these parameters in control group (p <0.05). There was significant difference in plasma levels of CRP, insulin and total NO metabolite between two groups of experiment. Negative significant correlation of CRP and insulin also was observed in HC rabbits (r = -0.99, p <0.05). Parallel NOx and insulin increment and negative correlation of CRP and insulin in HC rabbits may be suggestive a protective role of hyperinsulinemia in early atherosclerosis.
    Full-text · Article · Aug 2012 · Journal of Diabetes and Metabolic Disorders
  • Source

    Preview · Article ·
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is well known that CR (caloric restriction) reduces oxidative damage to proteins, lipids and DNA, although the underlying mechanism is unclear. However, information concerning the effect of CR on the host response to infection is sparse. In this study, 6-month-old mice that were fed AL (ad libitum) or with a CR diet were infected with Salmonella serovar Typhimurium. EPR (electron paramagnetic resonance; also known as ESR (electron spin resonance)) was used to identify FRs (free radicals). These results were subsequently correlated with SOD (superoxide dismutase) catalytic activity, iNOS [inducible NOS (nitric oxide synthase) or NOSII] expression and NO (nitric oxide) content. EPR analysis of liver samples demonstrated that there was a higher quantity of FRs and iron-nitrosyl complex in infected mice provided with a CR diet as compared with those on an AL diet, indicating that CR was beneficial by increasing the host response to Salmonella Typhimurium. Furthermore, in infected mice on the CR diet, NOSII expression was higher, NO content was greater and spleen colonization was lower, compared with mice on the AL diet. No changes in SOD activity were detected, indicating that the NO produced participated more in the formation of iron-nitrosyl complexes than peroxynitrite. These results suggest that CR exerts a protective effect against Salmonella Typhimurium infection by increasing NO production.
    Full-text · Article · Sep 2010 · Bioscience Reports
Show more