High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice.
OBJECTIVE
High-salt diet likely elevates blood pressure (BP), thus increasing the risk of cardiovascular events. We hypothesized that a high-salt diet plays a critical role in subjects whose renin-angiotensin systems cannot adjust to variable salt intake, rendering them more susceptible to atherosclerosis.


METHODS
Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We used urinary isoprostane as a marker for oxidative stress.


RESULTS
Although high-salt diet per se did not affect plaque extension, high salt combined with Ang II increased plaque area significantly in both the aorta and the innominate artery as compared with Ang II or salt alone (P < 0.05 and P < 0.01, respectively). High-salt diet did not affect BP or isoprostane levels, whereas Ang II infusion increased both BP and isoprostane levels (P < 0.05 and P < 0.01, respectively). Although high-salt diet combined with Ang II did not amplify BP, salt in combination with Ang II increased isoprostane levels further (P < 0.001 vs. Ang II alone). Ang II increases macrophage content in lesions (P < 0.05), whereas salt likely increases collagen content.


CONCLUSIONS
High-salt diet per se does not influence BP in ApoE-/- mice and is only moderately atherogenic. Possibly mediated via increased oxidative stress, a high-salt diet combined with fixed high Ang II levels accelerates atherogenesis synergistically, beyond the effect of BP.
Johansson
Maria E
ME
Department of Molecular and Clinical Medicine, Clinical Physiology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Bernberg
Evelina
E
Andersson
Irene J
IJ
Bie
Peter
P
Skøtt
Ole
O
Gan
Li-ming
LM
Bergström
Göran
G
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology*; D016122:Brachiocephalic Trunk / Q000473:pathology; D005260:Female; D008055:Lipids / Q000097:blood; D051379:Mice; D018384:Oxidative Stress; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
D001057:Apolipoproteins E; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II