title: Comparison between the effects of mixed dyslipidaemia and hypercholesterolaemia on endothelial function, atherosclerotic lesions and fibrinolysis in rabbits.
abstract: We compared the impact of hypercholesterolaemia and mixed dyslipidaemia on vascular function, vascular structure and fibrinolytic balance in rabbits. To this end, vascular reactivity was studied in aortic rings from rabbits fed a control diet, a diet containing 0.5% cholesterol+14% coconut oil (mixed dyslipidaemia) or a diet containing 1% cholesterol (hypercholesterolaemia) for 12-14 weeks. Morphometric analysis of aorta was also performed and plasminogen activator inhibitor-1 (PAI-1) as well as tissue-type plasminogen activator (t-PA) plasma activities were measured. Both diets induced a similar increase in cholesterol plasma levels, although triacylglycerols (triglycerides) were increased in animals with mixed dyslipidaemia. Hypercholesterolaemia was associated with intimal thickening, reduction in acetylcholine-induced relaxation ( P <0.05) and increased vasoconstriction induced by acetylcholine+ N (G)-nitro-L-arginine methyl ester (L-NAME) when compared with controls ( P <0.05). These effects were more marked ( P <0.05) in animals with mixed dyslipidaemia. Incubation with ifetroban, a thromboxane A(2)/prostaglandin H(2) receptor antagonist, increased acetylcholine-induced relaxation ( P <0.05) and reduced acetylcholine+L-NAME contraction ( P <0.05) in both diet groups. In contrast, the presence of PD 145, an endothelin (ET)(A)/ET(B) receptor antagonist, exerted these effects only in rabbits with mixed dyslipidaemia. Both hypercholesterolaemia and mixed dyslipidaemia induced a similar increase in PAI-1 and a similar decrease in t-PA plasma activities. These data suggest that hypertriglyceridaemia can increase the deleterious effects of hypercholesterolaemia on endothelial function and vascular structure. This additional harmful effect exerted by triacylglycerols on endothelial function could, in part, be mediated by ET.
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.forename: Eva
authors.initials: E
authors.lastname: Cediel
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Oubiña
authors.forename: Paloma
authors.initials: P
authors.lastname: Aragoncillo
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rosa
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004032:Diet; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors; D005342:Fibrinolysis; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D006949:Hyperlipidemias / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D015228:Hypertriglyceridemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010080:Oxazoles; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011817:Rabbits; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014662:Vasoconstrictor Agents
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D010080:Oxazoles; D017395:Plasminogen Activator Inhibitor 1; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; C078904:ifetroban; D019001:Nitric Oxide Synthase; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester