No abstract

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.

Of the classical risk factors, hypertension and diabetes mellitus were independently associated with early CAD. In addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. An additive effect of the APO AI-CIII genes was observed in triglyceride levels.

Renin-angiotensin system activation is recognized to play an important role in atherosclerosis. This study aimed to verify the antiatherosclerotic effects of ACE inhibition on an experimental model of diabetes and hypercholesterolemia. Diabetes was induced in New Zealand male rabbits with a single dose of alloxan (100 mg/kg, i.v.), and, according to plasma glucose levels obtained after 1 week, the animals were divided into 2 groups (> or =250 mg/dL or <250 mg/dL). Each group was randomly assigned to receive or not quinapril (30 mg/d) added to a 0.5% cholesterol-enriched diet. Animals with high glucose levels at 1 week and that remained high after 12 weeks presented higher triglyceride levels (P < 0.02 versus basal). Those initially hyperglycemic but presenting <250 mg/dL glucose at the end of study formed an additional group. Plasma ACE activity was lower in quinapril-treated animals (P < 0.01 versus untreated groups). However, aorta intima/media ratio and intima area were lower only in the subgroups of quinapril-treated animals with low glucose levels (P < 0.05). Our results support the hypothesis that high plasma glucose may abolish the antiatherosclerotic effect of ACE inhibitors.