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+NG-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 A2/prostaglandin H2 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/ETB 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.
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March 06 2003
Comparison between the effects of mixed dyslipidaemia and hypercholesterolaemia on endothelial function, atherosclerotic lesions and fibrinolysis in rabbits Available to Purchase
Natalia de las HERAS;
Natalia de las HERAS
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
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Eva CEDIEL;
Eva CEDIEL
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
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M. Pilar OUBIÑA;
M. Pilar OUBIÑA
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
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Paloma ARAGONCILLO;
Paloma ARAGONCILLO
†Department of Pathology, Unit II, Hospital Clínico San Carlos, Madrid 28040, Spain
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David SANZ-ROSA;
David SANZ-ROSA
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
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Vicente LAHERA;
Vicente LAHERA
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
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Victoria CACHOFEIRO
*Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain
Correspondence: Dr V. Cachofeiro (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
July 18 2002
Revision Received:
November 11 2002
Accepted:
January 10 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2003
2003
Clin Sci (Lond) (2003) 104 (4): 357–365.
Article history
Received:
July 18 2002
Revision Received:
November 11 2002
Accepted:
January 10 2003
Citation
Natalia de las HERAS, Eva CEDIEL, M. Pilar OUBIÑA, Paloma ARAGONCILLO, David SANZ-ROSA, Vicente LAHERA, Victoria CACHOFEIRO; Comparison between the effects of mixed dyslipidaemia and hypercholesterolaemia on endothelial function, atherosclerotic lesions and fibrinolysis in rabbits. Clin Sci (Lond) 1 April 2003; 104 (4): 357–365. doi: https://doi.org/10.1042/cs1040357
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