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Research article

Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

Anna K.J. Gradel, Max Salomonsson, Charlotte M. Sørensen, Niels-Henrik Holstein-Rathlou, Lars Jørn Jensen
Clinical Science Feb 28, 2018, 132 (4) 461-474; DOI: 10.1042/CS20171408
Anna K.J. Gradel
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Max Salomonsson
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkMedical Ward 12, Trelleborg Hospital, Trelleborg, Sweden
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Charlotte M. Sørensen
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Niels-Henrik Holstein-Rathlou
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Lars Jørn Jensen
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • For correspondence: Lajj@sund.ku.dk
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Abstract

Abdominal obesity and/or a high intake of fructose may cause hypertension. K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K+ transporters in long-term diet-induced hypertension in rats. We hypothesized that a 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Male Sprague–Dawley (SD) rats received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from the age of 4 weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries (SMAs). BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of small conductance calcium-activated K+ channel (SKCa), intermediate conductance calcium-activated K+ (IKCa), and Kir2.1 inward rectifier K+ channels were reduced in the High Fat/Fruc group. Reduced endothelium-derived hyperpolarization (EDH)-type relaxation to acetylcholine (ACh) was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all the experimental diet groups. In conclusion, reduced expression and function of SKCa, IKCa, and Kir2.1 channels are associated with elevated blood pressure in rats fed a long-term High Fat/Fruc. Rats fed a 28-week High Fat/Fruc provide a relevant model of diet-induced hypertension.

  • hypertension
  • diet-induced obesity
  • potassium channels
  • small arteries
  • vascular tone
  • Abbreviations

    ACh,
    acetylcholine;
    ActB,
    β-actin reference gene;
    AUC,
    area under curve;
    BKCa,
    big conductance calcium-activated K+ channel;
    BW,
    body weight;
    EC,
    endothelial cell;
    EC50,
    half-maximal effective concentration;
    EDH,
    endothelium-derived hyperpolarization;
    FMVD,
    flow-mediated vasodilatation;
    IKCa,
    intermediate conductance calcium-activated K+ channel;
    Kir2.1,
    inward rectifier K+ channel subtype 2.1;
    L-NAME,
    Nω-Nitro-L-arginine methyl ester hydrochloride;
    MAP,
    mean arterial blood pressure;
    NE,
    norepinephrine;
    NO,
    nitric oxide;
    PE,
    phenylephrine;
    PSS,
    physiological saline solution;
    PGI2,
    prostacyclin;
    Q-PCR,
    quantitative real-time PCR;
    SBP,
    systolic blood pressure;
    SD,
    Sprague–Dawley;
    SKCa,
    small conductance calcium-activated K+ channel;
    SMA,
    small mesenteric artery;
    TPR,
    total peripheral resistance;
    VSMC,
    vascular smooth muscle cell
    • © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    February 2018

    Volume: 132 Issue: 4

    Clinical Science: 132 (4)
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    Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels
    Anna K.J. Gradel, Max Salomonsson, Charlotte M. Sørensen, Niels-Henrik Holstein-Rathlou, Lars Jørn Jensen
    Clinical Science Feb 2018, 132 (4) 461-474; DOI: 10.1042/CS20171408
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    Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels
    Anna K.J. Gradel, Max Salomonsson, Charlotte M. Sørensen, Niels-Henrik Holstein-Rathlou, Lars Jørn Jensen
    Clinical Science Feb 2018, 132 (4) 461-474; DOI: 10.1042/CS20171408

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    Keywords

    Hypertension
    diet-induced obesity
    potassium channels
    small arteries
    vascular tone

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