The protective role of atorvastatin on function, structure and ultrastructure in the aorta of dyslipidemic rabbits

Abstract

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.

Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits

“…Lesion area was determined by tracing in digitalized segmentedcoloured sections stained with Masson trichrome using a QWIN Leica image analyser (Leica Imaging Systems Ltd, Cambridge, U.K.) as described previously [3,5,21]. In order to determine the luminal area or the vessel area, the cross-sectional area enclosed by the internal or external elastic lamina respectively, was corrected to a circle by applying the form factor (l 2 / 4π ) to the measurement of the lamina, where l is the length of the lamina.…”

“…Descending thoracic aorta was excised from pentobarbital-anaesthetized animals and processed as described previously [3,5]. The vasorelaxing response to either an endothelium-dependent (acetylcholine; 10 −9 -10 −5 mol/l) or -independent (sodium nitroprusside; 10 −10 -10 −6 mol/l) vasodilator was studied in aortic rings from normolipidaemic and dyslipidaemic rabbits precontracted with a submaximal dose of phenylephrine (10 −6 mol/l).…”

“…Antihypertensive and hypolipidaemic drugs, such as angiotensin-converting enzyme (ACE) inhibitors and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, exert beneficial effects on both the development and complications of atherosclerosis [3,[16][17][18][19]. However, there is not enough data comparing, in an integrated manner, the effects of statins and ACE inhibitors on the vascular and functional alterations associated with early phases of atherosclerosis.…”

“…Endothelial dysfunction is a common consequence of hypercholesterolaemia and has usually been characterized by an impairment of endothelium-dependent relaxations [2][3][4][5]. However, endothelial dysfunction not only involves changes in the endothelial regulation of vascular tone, but also changes in vascular smooth muscle cell growth, leucocyte adhesion, platelet function and fibrinolytic activity [4][5][6].…”

“…Hypercholesterolaemia produces numerous functional and structural alterations in the vascular wall and leads to the development of atherosclerosis [1][2][3][4][5], which is the major cause of morbidity and mortality in western populations. Endothelial dysfunction is a common consequence of hypercholesterolaemia and has usually been characterized by an impairment of endothelium-dependent relaxations [2][3][4][5].…”