[Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits].
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 At the end of the experiment, a blood sample was withdrawn for determining total cholesterol and separating the lipoproteins, and a segment of the thoracic aorta was removed to be used for studying endothelial function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.


CONCLUSIONS
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.
Jorge
Paulo Afonso Ribeiro
PA
Faculdade de Ciências Médicas, Unicamp, Campinas, SP. parjorge@terra.com.br
Almeida
Eros Antonio de
EA
Ozaki
Michiko R
MR
Jorge
Mariana
M
Carneiro
Adriano
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001018:Aortic Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D007211:Indoles; D011758:Pyrroles; D000077340:Fluvastatin; D008315:Malondialdehyde; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin