title: Early benefits of pravastatin to experimentally induced atherosclerosis.
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.
authors.affiliation: Federal University of Sao Paulo, SP, Brazil.
authors.forename: Eliane P
authors.initials: EP
authors.lastname: Silva
authors.forename: Francisco A H
authors.initials: FA
authors.lastname: Fonseca
authors.forename: Silvia S M
authors.initials: SS
authors.lastname: Ihara
authors.forename: Maria C O
authors.initials: MC
authors.lastname: Izar
authors.forename: Ieda L
authors.initials: IL
authors.lastname: Lopes
authors.forename: Leonor E S A
authors.initials: LE
authors.lastname: Pinto
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: Sergio
authors.initials: S
authors.lastname: Tuffik
authors.forename: Therezinha B
authors.initials: TB
authors.lastname: Paiva
authors.forename: Nelson
authors.initials: N
authors.lastname: Kasinski
authors.forename: Angelo V
authors.initials: AV
authors.lastname: de Paola
authors.forename: Antonio C C
authors.initials: AC
authors.lastname: Carvalho
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D002784:Cholesterol; D017035:Pravastatin; D000109:Acetylcholine