There is little information regarding the time of hypolipidemic treatment of changes in
atherosclerotic plaque, tissue
cholesterol content, and also for the recovery of endothelial function. To assess the early effects of
lipid-lowering treatment on these parameters, six groups of New Zealand male rabbits were studied. Animals in groups I and II were fed regular chow; groups III and IV received a 12-week 0.5%
cholesterol diet followed by 12 weeks of 0.05%
cholesterol diet. Finally, groups V and VI were fed a 12-week 0.5%
cholesterol diet and were then shifted to a regular diet for 12 weeks. During the last four weeks, the rabbits in groups I, III, and V received low-dose
pravastatin (2 mg/day), added to the diet. Group IV animals had the highest
cholesterol plasma levels (vs. groups I, II, III, and V, p < 0.01) and presented
atherosclerotic plaques in a more advanced stage. Nonatherogenic diet was insufficient to restore endothelial function in animals previously fed
cholesterol-enriched diets (groups IV and VI). Conversely,
pravastatin treatment promoted significant improvement in endothelial function and reduced the progression of
atherosclerosis. Marked increase in
cholesterol content was seen in aorta and liver in response to the atherogenic diet. However, neither treatment with
pravastatin nor nonatherogenic diet was capable of modifying the tissue
cholesterol content. Our study supports the hypothesis that the early use of
statins can attenuate the progression of
atherosclerosis and ameliorate endothelial function. In addition, significant changes in the tissue
cholesterol pool probably need a longer period of treatment.