High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E-deficient mice

    Research output: Contribution to journalArticleScientificpeer-review

    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.
    Original languageEnglish
    JournalBlood Pressure
    Volume14
    Pages (from-to)373-382
    Number of pages10
    ISSN0803-7051
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Cite this

    @article{91218b34c31043838b43cac073742431,
    title = "High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E-deficient mice",
    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.",
    author = "Juha Ketonen and Saara Merasto and Ilari Paakkari and Eero Mervaala",
    year = "2005",
    doi = "10.1080/08037050500383687",
    language = "English",
    volume = "14",
    pages = "373--382",
    journal = "Blood Pressure",
    issn = "0803-7051",
    publisher = "TAYLOR & FRANCIS LTD",

    }

    High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E-deficient mice. / Ketonen, Juha; Merasto, Saara; Paakkari, Ilari; Mervaala, Eero.

    In: Blood Pressure, Vol. 14, 2005, p. 373-382.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E-deficient mice

    AU - Ketonen, Juha

    AU - Merasto, Saara

    AU - Paakkari, Ilari

    AU - Mervaala, Eero

    PY - 2005

    Y1 - 2005

    N2 - 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.

    AB - 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.

    U2 - 10.1080/08037050500383687

    DO - 10.1080/08037050500383687

    M3 - Article

    VL - 14

    SP - 373

    EP - 382

    JO - Blood Pressure

    JF - Blood Pressure

    SN - 0803-7051

    ER -