Effects of Indapamide on Atherosclerosis Development in Cholesterol-Fed Rabbits

Río, Marcela Del; Chulia, Teresa; Merchán-Pérez, Ángel; Remezal, Manuel; Valor, S; González, Julio L. Álvarez; Gutiérrez, Jorge; Contreras, Jaime; Lasunción, M.A.; Tejerina, Teresa

doi:10.1097/00005344-199506000-00017

Cited by 15 publications

(5 citation statements)

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“…The atheromatose lesions in this animal are similar to those in humans also in sequence, as confirmed en aortic atherosclerosis [116], making this animal a universal model for studying the anti-atherogenic activity of many drugs [117][118][119][120]. For the characteristics detailed below, the New Zealand rabbit is an excellent model to reproduce human atheromatosis because: i) it is possible to induce hypercholesterolaemia in a few days after administration of a highcholesterol diet [121]; ii) it is sensitive to the induction of atheromatose lesions [116]; iii) hypercholesterolaemia results from excess LDL [122]; iv) excess cholesterol is eliminated from the tissues to be incorporated in high-density lipoproteins (HDL) [4]; vi) it is capable of forming cholesterol-HDL complexes associated with apoE which are transported by the blood to the liver [4]; vii) the lipoprotein profile is similar in size to that of humans in the highest range, with HDl being practically the same [123]; viii) it presents postprandial hyperlipaemia for the existence of chilomicron remnants [124]; ix) the hyperlipaemic diet increases apoE [125]; and x) the sustained alteration of lipids after feeding with a cholesterolrich diet is reversible when the diet is replaced by a normal one [121].…”

Section: Rabbitssupporting

confidence: 57%

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sebastián¹,

Corral²,

Montañana³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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Section: Rabbitssupporting

confidence: 57%

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sebastián¹,

Corral²,

Montañana³

et al. 2012

Current Basic and Pathological Approaches to the Function of Muscle Cells and Tissues - From Molecules to Humans

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“…Animals were individually housed at 25°C and exposed to a daily 12-hour/12-hour light/dark cycle. We 8 and others 9,10 have reported that the oral dosage of IND required to normalize BP in SHR is Ͼ1.5 mg · kg Ϫ1 · d…”

mentioning

confidence: 87%

Sodium Intake, Large Artery Stiffness, and Proteoglycans in the Spontaneously Hypertensive Rat

et al. 2001

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Abstract-Although the role of sodium in hypertension has been documented extensively, its effect on large arteries has not been well documented. We examined the effect of high-sodium (8%) diet and the diuretic indapamide (IND) on systemic hemodynamics and aortic wall structure and composition in collagen, elastin, and hyaluronan. Four groups of spontaneously hypertensive rats (SHR) were studied after 8 weeks: those on a normal diet (SHR), a high-sodium diet (SHRϩNaCl), a normal diet with IND (SHRϩIND), and a high-sodium diet with IND (SHRϩNaClϩIND). Mean BP, which was not normalized with IND, was comparable for all groups. Systemic arterial compliance averaged 3.8, 2.5, 4.9, and 3.3 mL/mm Hg · 10 Ϫ3 , respectively, for the SHR, SHRϩNaCl, SHRϩIND, and SHRϩNaClϩIND groups (PϽ0.003 and Ͻ0.05 for NaCl and IND effects). Wall thickness increased only in the SHRϩNaCl group (PϽ0.01). Aortic wall COL decreased from 16 116 in the SHR to 12 382 m 2 /mm in the SHRϩNaClϩIND (PϽ0.005) group. IND alone had no effect on elastin, but the elastin/collagen ratio was increased significantly. Aortic hyaluronan averaged 2343, 266, 3243, and 1052 m 2 /mm, respectively, for the SHR, SHRϩNaCl, SHRϩIND, and SHRϩNaClϩIND groups (PϽ0.0001 for NaCl and IND effects). Changes in systemic arterial compliance were significantly and positively correlated with aortic hyaluronan contents. Thus, high-sodium diet affects the structural and functional characteristics of large arteries independently of BP. A high-sodium diet, in addition to a diuretic regimen with IND, affects simultaneously aortic hyaluronan contents and large artery mechanical properties through pressure-independent mechanisms that remain to be defined. Key Words: arteries Ⅲ diet Ⅲ diuresis Ⅲ proteoglycans Ⅲ rats, spontaneously hypertensive E pidemiological studies indicate that in populations of normotensive and hypertensive subjects, a strong association is observed between high sodium intake and increased aortic rigidity, independent of both age and BP level. 1 Conversely, reduced sodium intake is associated with enhanced arterial elasticity. 2 In hypertensive rats, high sodium intake leads not only to cardiac hypertrophy and fibrosis but also to hypertrophy of large arteries and enhanced extracellular matrix, again independently of BP level. 3 However, the potential link between such structural alterations and the mechanical properties of the arteries has not been investigated extensively.During high sodium intake in experimental animals, concentration of this cation in the vascular smooth muscle cell rises, but most of it remains extracellularly bound to the interstitial matrix, probably to polyanionic mucopolysaccharides. 4 To our knowledge, whether such macromolecules contribute to mechanical properties of the arteries during high sodium intake has never been reported under in vivo conditions, at least for large conduit arteries. In sodium-dependent hypertensive animal models, diuretics reduce hypertrophy of the arterial wall even if BP remains unchanged. 2 Interestingly, a c...

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“…Investigation has continued on hypercholesterolaemic rabbits since 1913, when Anitschkow demonstrated that, in rabbits fed a hypercholesterolaemic diet underwent atherosclerotic changes at the level of the arterial intima similar to those in atherosclerotic humans. The atheromatose lesions in this animal are similar to those in humans also in sequence, as Effects of Hypercholesterolaemia in the Retina 13 confirmed in aortic atherosclerosis [3], making this animal a universal model for studying the anti-atherogenic activity of many drugs [129][130][131][132].…”

Section: Rabbitsmentioning

confidence: 97%

“…For the characteristics detailed below, the New Zealand rabbit is an excellent model to reproduce human atheromatosis because: i) it is possible to induce hypercholesterolaemia in a few days after administration of a high-cholesterol diet [2]; ii) it is sensitive to the induction of atheromatose lesions [3]; iii) hypercholesterolaemia results from excess LDL [133]; iv) excess cholesterol is eliminated from the tissues to be incorporated in HDL [134]; vi) it is capable of forming cholesterol-HDL complexes associated with apoE which are transported by the blood to the liver [134]; vii) the lipoprotein profile is similar in size to that of humans in the highest range, with HDL being practically the same [135]; viii) it presents postprandial hyperlipaemia for the existence of chilomicron remnants [136]; ix) the hyperlipaemic diet increases apoE [4]; and x) the sustained alteration of lipids after feeding with a cholesterol-rich diet is reversible when the diet [130] is replaced by a normal one [2].…”

Section: Rabbitsmentioning

confidence: 99%

Effects of Hypercholesterolaemia in the Retina

Casado¹,

López²,

Sebastián³

et al. 2012

Ocular Diseases

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The changes in the RPE-Bruch's membrane complex contribute to the death of multiple retinal neurons, this translating as a thinning and disorganization of its layers.Cholesterol is essential for cell functioning. The main cholesterol source for the photoreceptors and the RPE comes from extracellular lipid metabolism, as has been demonstrated on detecting native low-density lipoprotein (LDL) receptors at the RPE level [12], which could be involved in the local production of apolipoprotein E (apoE). The retina also locally produces lipoprotein particles that contain apoE. These particles are secreted fundamentally by the Müller glia to the extracellular retinal compartment and to the vitreous, from which they are transported to the optic nerve [13]. Also, the retinal astrocytes associated with the axons of the ganglion cells participate in the secretion of apoE. This cholesterol transport is essential to supply the retinal neurons the lipids needed for the maintenance and remodelling of their cell membrane.

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Effects of Indapamide on Atherosclerosis Development in Cholesterol-Fed Rabbits

Cited by 15 publications

References 0 publications

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Choroidal Vessel Wall: Hypercholesterolaemia-Induced Dysfunction and Potential Role of Statins

Sodium Intake, Large Artery Stiffness, and Proteoglycans in the Spontaneously Hypertensive Rat

Effects of Hypercholesterolaemia in the Retina

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