Activation of the Renin-Angiotensin system mediates the effects of dietary salt intake on atherogenesis in the apolipoprotein E knockout mouse.
Hypertension
; 60(1): 98-105, 2012 Jul.
Article
en En
| MEDLINE
| ID: mdl-22647892
ABSTRACT
Dietary salt intake is a major determinant of the activation state of renin-angiotensin-aldosterone system. Given the important role of the renin-angiotensin-aldosterone system in plaque accumulation, we investigated its role in the development of atherogenesis associated with sodium intake in apolipoprotein E knockout mice. Six-weeks of a low-salt diet (containing 0.03% sodium) resulted in a 4-fold increase in plaque accumulation in apolipoprotein E knockout mice when compared with mice receiving normal chow (containing 0.30% sodium). This was associated with activation of the renin-angiotensin-aldosterone system, increased vascular expression of adhesion molecules and inflammatory cytokines, and increased adhesion of labeled leukocytes across the whole aorta on a dynamic flow assay. These changes were blocked with the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg per day). A high-salt diet (containing 3% sodium) attenuated vascular inflammation and atherogenesis, associated with suppression of the renin-angiotensin-aldosterone system, although systolic blood pressure levels were modestly increased (5 ± 1 mmHg). Constitutive activation of the renin-angiotensin-aldosterone system in angiotensin-converting enzyme 2 apolipoprotein E knockout mice was also associated with increased atherosclerosis and vascular adhesion, and this was attenuated by a high-salt diet associated with suppression of the renin-angiotensin-aldosterone system. By contrast, a low-salt diet failed to further activate the renin-angiotensin-aldosterone system or to increase atherosclerosis in angiotensin-converting enzyme 2 apolipoprotein E knockout mice. Together, these data validate a relationship between salt-mediated renin-angiotensin-aldosterone system activation and atherogenesis, which may partly explain the inconclusive or paradoxical findings of recent observational studies, despite clear effects on blood pressure.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteínas E
/
Sistema Renina-Angiotensina
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Cloruro de Sodio Dietético
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Aterosclerosis
Tipo de estudio:
Observational_studies
Idioma:
En
Revista:
Hypertension
Año:
2012
Tipo del documento:
Article
País de afiliación:
Australia