Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits

Abstract

Objective: To compare the effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, aortic atherosclerosis, and the content of malondialdehyde (MDA) in native and oxidized LDL and in the arterial wall of hypercholesterolemic rabbits after adjusting the dosages of those statins to reduce total serum cholesterol levels to similar values. Methods: Male rabbits were divided into the following 6 groups of 10 animals (n=10): 1) GH (control) - hypercholesterolemic animals; 2) GA - atorvastatin; 3) GF - fluvastatin; 4) GP - pravastatin; 5) GS - simvastatin; and 6) GN - normal. The animals were fed a standard food preparation enriched with 0.5% cholesterol and 2% coconut oil for 45 days. Fifteen days after beginning the experiment, atorvastatin, fluvastatin, pravastatin and simvastatin were administered for 15 days through gavage, and the dosages were adjusted to obtain similar cholesterol values in each group. At the end of the experiment, a blood sample was withdrawn for determining total cholesterol and separating the lipoproteins, and a segment of the thoracic aorta was removed to be used for studying endothelial function and lipid peroxidation, and for measuring aortic atherosclerosis in histological sections. Results: The statins significantly reduced total serum cholesterol levels, LDL-cholesterol levels, and aortic atherosclerosis. The MDA content was also significantly reduced in native and oxidized LDL, as well as in the arterial wall. Endothelium-dependent relaxation was significantly greater in the treated group compared with that in the hypercholesterolemic group. Conclusion: The statins, at dosages adjusted, had a significant and similar effect in reducing lipid peroxidation in native and oxidized LDL-C and in arterial walls, in decreasing aortic atherosclerosis, and in reverting endothelial dysfunction.