The protective role of atorvastatin on function, structure and ultrastructure in the aorta of dyslipidemic rabbits.
Responses to both an endothelium-dependent (acetylcholine 10(-9)-10(-5) mol/l) and an endothelium-independent vasodilator (sodium nitroprusside 10(-10)-10(-6) mol/l) were studied in aortic rings from rabbits fed or not with a diet containing 0.5% cholesterol plus 14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg/kg/day). Morphometric and ultrastructure analyses were also performed. Rabbits fed the dyslipidemic diet presented higher plasma cholesterol and triglyceride concentrations than controls (P < 0.05). This was associated with intima-media thickening and, consequently, aortic stenosis (29 +/- 3%) since vessel cross-sectional area did not change. Endothelial cells presented numerous alterations in dyslipidemic rabbits. Atorvastatin treatment only reduced plasma levels in dyslipidemic rabbits (P < 0.05), which were nevertheless higher than those of controls. In addition, it prevented the reduction in acetylcholine relaxation in hypercholesterolemic animals. Atorvastatin administration also enhanced the response to acetylcholine in rabbits fed a control diet. Likewise, atorvastatin treatment reduced lesion area and consequently increased aortic lumen in dyslipidemic rabbits but did not modify media thickening. It also prevented the majority of the ultrastructural changes observed in endothelial cells. In conclusion, chronic atorvastatin treatment exerts a protective role in vascular function, structure and ultrastructure even in the presence of high cholesterol and triglyceride plasma levels.
Aragoncillo
P
P
Pathology Department, Unit II, Hospital Clínico San Carlos, Spain.
Maeso
R
R
Vázquez-Pérez
S
S
Navarro-Cid
J
J
Ruilope
L M
LM
Díaz
C
C
Hernández
G
G
Lahera
V
V
Cachofeiro
V
V
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin