Dietary salt restriction accelerates atherosclerosis in apolipoprotein E-deficient mice.
BACKGROUND
Whether a general reduction in salt intake reduces or actually enhances cardiovascular mortality in man remains an issue of controversy. Low sodium diets may lead to adverse side effects by stimulating the renin-angiotensin and sympathetic nervous systems. The present study was designed to investigate the effects of low dietary salt on atherosclerotic lesion progression in apolipoprotein E deficient (apoE(-/-)) mice.


RESULTS
We fed 7-week-old apoE(-/-) mice on low (0.036% NaCl; n=28) or regular (0.64% NaCl; n=26) salt diets for 16 weeks. At the age of 23 weeks, the cross-section surface area of atherosclerotic plaques was measured in aortic root and thoracic aorta. Serum total cholesterol, triglycerides, plasma angiotensin levels and urinary protein/creatinine concentrations were assessed. Exposure to low salt caused significant increases in atherosclerotic lesion surface area in thoracic aorta, but did not alter lesion area in aortic root. Low-salt mice also had higher serum total cholesterol and higher plasma angiotensin II (ANG-II) concentrations. Atherosclerotic lesion area was correlated with ANG-II levels in low-salt but not in regular-salt animals, and with total cholesterol concentration in all mice. Mean arterial pressure was comparable in both groups.


CONCLUSIONS
Dietary salt restriction accelerated atherosclerotic lesion formation in apoE(-/-) mice through a mechanism that is probably related to ANG-II formation. Whether these findings are relevant to human cardiovascular disease remains to be evaluated.
Ivanovski
Ognen
O
INSERM Unit 507, Necker Hospital, 161 Rue de Sèvres, 75015 Paris, France. ivanovski@necker.fr
Szumilak
Dorota
D
Nguyen-Khoa
Thao
T
Dechaux
Michele
M
Massy
Ziad A
ZA
Phan
Olivier
O
Mothu
Nadya
N
Lacour
Bernard
B
Drueke
Tilman B
TB
Muntzel
Martin
M
D000804:Angiotensin II / Q000096:biosynthesis / Q000502:physiology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000503:physiopathology* / Q000662:veterinary; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012084:Renin-Angiotensin System / Q000502:physiology; D012982:Sodium, Dietary
D001057:Apolipoproteins E; D012982:Sodium, Dietary; D000804:Angiotensin II