Activation of the Renin-Angiotensin system mediates the effects of dietary salt intake on atherogenesis in the apolipoprotein E knockout mouse.

Content Provider	Semantic Scholar
Author	Tikellis, Chris Pickering, Raelene J. Tsorotes, Despina Huet, Olivier Jacqueline Chin-Dusting, Jaye P. F. Cooper, Mark Thomas, Merlin C.
Copyright Year	2012
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.
Starting Page	98
Ending Page	105
Page Count	8
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://hyper.ahajournals.org/content/hypertensionaha/60/1/98.full.pdf?download=true
Alternate Webpage(s)	http://hyper.ahajournals.org/content/hypertensionaha/60/1/98.full.pdf
Alternate Webpage(s)	http://hyper.ahajournals.org/content/hypertensionaha/early/2012/05/28/HYPERTENSIONAHA.112.191767.full.pdf
PubMed reference number	22647892v1
Alternate Webpage(s)	https://doi.org/10.1161/HYPERTENSIONAHA.112.191767
DOI	10.1161/hypertensionaha.112.191767
Journal	Hypertension
Volume Number	60
Issue Number	1
Language	English
Access Restriction	Open
Subject Keyword	ACE protein, human Activation action Aldosterone Angiotensin-Converting Enzyme Inhibitors Angiotensins Aorta Apolipoproteins Atherogenesis Atherosclerosis CNS disorder Cerebrovascular Disorders Data Table Dental Plaque Elfacos OW 100 Falco columbarius Heart Diseases Heart failure Html Link Type - copyright Hyperactive behavior Hypertensive disease Low sodium diet Mice, Knockout Perindopril Renin-angiotensin system Request - action Scientific Publication Senile Plaques Sodium Chloride, Dietary Tracer angiotensin converting enzyme 2 chow chow cytokine salt intake torr
Content Type	Text
Resource Type	Article