Differential effects of dietary sodium intake on blood pressure and atherosclerosis in hypercholesterolemic mice.
The amount of dietary sodium intake regulates the renin angiotensin system (RAS) and blood pressure, both of which play critical roles in atherosclerosis. However, there are conflicting findings regarding the effects of dietary sodium intake on atherosclerosis. This study applied a broad range of dietary sodium concentrations to determine the concomitant effects of dietary sodium intake on the RAS, blood pressure, and atherosclerosis in mice. Eight-week-old male low-density lipoprotein receptor -/- mice were fed a saturated fat-enriched diet containing selected sodium concentrations (Na 0.01%, 0.1%, or 2% w/w) for 12 weeks. Mice in these three groups were all hypercholesterolemic, although mice fed Na 0.01% and Na 0.1% had higher plasma cholesterol concentrations than mice fed Na 2%. Mice fed Na 0.01% had greater abundances of renal renin mRNA than those fed Na 0.1% and 2%. Plasma renin concentrations were higher in mice fed Na 0.01% (14.2 ± 1.7 ng/ml/30 min) than those fed Na 0.1% or 2% (6.2 ± 0.6 and 5.8 ± 1.6 ng/ml per 30 min, respectively). However, systolic blood pressure at 12 weeks was higher in mice fed Na 2% (138 ± 3 mm Hg) than those fed Na 0.01% and 0.1% (129 ± 3 and 128 ± 4 mmHg, respectively). In contrast, mice fed Na 0.01% (0.17 ± 0.02 mm(2)) had larger atherosclerotic lesion areas in aortic roots than those fed Na 2% (0.09 ± 0.01 mm(2)), whereas lesion areas in mice fed Na 0.1% (0.12 ± 0.02 mm(2)) were intermediate between and not significantly different from those in Na 0.01% and Na 2% groups. In conclusion, while high dietary sodium intake led to higher systolic blood pressure, low dietary sodium intake augmented atherosclerosis in hypercholesterolemic mice.
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536, USA.
Hong
H
Lu
Congqing
C
Wu
Deborah A
DA
Howatt
Anju
A
Balakrishnan
Richard J
RJ
Charnigo
Lisa A
LA
Cassis
Alan
A
Daugherty
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics; D012083:Renin / Q000097:blood / Q000235:genetics; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000009:adverse effects / Q000494:pharmacology*
D011973:Receptors, LDL; D012982:Sodium, Dietary; D000450:Aldosterone; D002784:Cholesterol; D012964:Sodium; D012083:Renin