LATE TREATMENT WITH L-ARGININE INCREASES ۸-ISOPROSTAGLANDIN F۲Α AND OXIDIZED LDL IN HYPERCHOLESTEROLEMIC RABBITS

Abstract    BACKGROUND: The role of L-arginine, the precursor of nitric oxide, on the oxidative stress and atherosclerosis has been previously studied; it has had inconsistent beneficial effects. The aim of this study was to investigate whether administration of L-arginine reduces oxidative stress and the progression of atherosclerosis in cholesterol fed rabbits.    METHODS: Eighteen white male rabbits were randomized into three groups. All of them received ۱% high cholesterol diet for the first four weeks and normal diet for the second four weeks of the experiment. The early treatment (ET) group received L-arginine (۳% in drinking water) in the first four weeks while the late treatment (LT) group received L-arginine for the second four weeks of the experiment. Control (C) group received no L-arginine. The plasma levels of lipids, ۸-isoprostaglandin F۲α, CRP and oxLDL were measured before, and at ۴th and ۸th weeks of the experiment. Aorta fatty streak formation was measured at the end of the experiment.    RESULTS: The plasma levels of lipids were increased significantly during the first ۴ weeks and decreased significantly during the second ۴ weeks with no significant differences between the groups. The plasma concentration of ۸-isoprostaglandin F۲α was significantly decreased in the ET group compared with the C group at the end of the experiment. The fatty streak formation in the ET group was significantly lower than that in the C group at the end of the experiment. The plasma concentration of CRP significantly increased after ۴ weeks administration of hypercholesterolemic diet in all groups. Also, its amount was significantly smaller in ET group in comparison with other groups. The plasma concentration of oxLDL decreased significantly in the ET group compared with LT group at the end of the experiment. However, the plasma concentration of oxLDL increased in the C group and in the LT group at the end of the experiment.    CONCLUSION: L-arginine therapy from the very beginning of hypercholesterolemia reduced oxidative stress and the consequential irreversible vascular damage, and may be useful for primary prevention.      Keywords: Atherosclerosis, Oxidized Low Density Lipoproteins, Oxidative Stress, ۸-Isoprostaglandin F۲α, L-Arginine, Nitric Oxide.