High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E‐deficient mice
- 1 January 2005
- journal article
- research article
- Published by Taylor & Francis in Blood Pressure
- Vol. 14 (6), 373-382
- https://doi.org/10.1080/08037050500383687
Abstract
Hypertension is a major risk factor for atherosclerosis. We tested the hypothesis whether high salt intake aggravates endothelial dysfunction and promotes atherosclerosis in apolipoprotein E‐deficient mice (ApoE−/− mice) and their littermate controls (C57Bl/6 mice). The role of increased oxidative stress was also examined. A high‐salt diet (NaCl 7%) for 12 weeks increased blood pressure and induced cardiac hypertrophy and albuminuria more pronouncedly in ApoE−/− mice compared with C57Bl/6. Endothelium‐dependent vascular relaxation in response to acetylcholine was almost maximally impaired in ApoE−/− mice during a normal sodium diet. A high‐salt diet did not further impair NO‐mediated vascular relaxation. A high‐salt diet also markedly attenuated endothelium‐dependent relaxation in C57Bl/6 mice. Preincubation with the superoxide scavenger Tiron normalized endothelial function almost completely in both mice strains indicating the central role of increased oxidative stress in the pathogenesis. Aortic superoxide production and the extent of atherosclerotic lesions were greater in ApoE−/− mice on a normal‐salt diet compared with C57Bl/6. The high‐salt diet increased vascular superoxide formation and promoted atherosclerosis in ApoE−/− mice. Changes in dietary salt intake did not influence serum lipids in either mouse strains. Our findings suggest a detrimental role for high salt intake in the development of atherosclerosis and underscore the importance of increased oxidative stress in the pathogenesis salt‐induced vascular damage.Keywords
This publication has 39 references indexed in Scilit:
- Nitric Oxide and the Regulation of Large Artery StiffnessHypertension, 2004
- Atorvastatin Prevents End-Organ Injury in Salt-Sensitive HypertensionHypertension, 2004
- Dysfunction of Endothelial Nitric Oxide Synthase and AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- Effect of high-salt diet on NO release and superoxide production in rat aortaAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- In Salt-Sensitive Hypertension, Increased Superoxide Production Is Linked to Functional Upregulation of Angiotensin IIHypertension, 2003
- Mechanism of Endothelial Dysfunction in Apolipoprotein E–Deficient MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2001
- Endothelial Dysfunction in Salt-Sensitive Essential HypertensionHypertension, 2001
- Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L -arginine-tetrahydrobiopterin and enhanced vasoconstriction by endothelinBritish Journal of Pharmacology, 2000
- Enhanced atherosclerosis and kidney dysfunction in eNOS–/–Apoe–/– mice are ameliorated by enalapril treatmentJCI Insight, 2000
- Clustering of Endothelial Markers of Vascular Damage in Human Salt-Sensitive HypertensionHypertension, 1998