Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion

DOI Web Site 被引用文献21件
  • Theodore L. Goodfriend
    From the William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology of the University of Wisconsin (T.L.G., D.L.B.); Madison; Department of Medicine (B.M.E.), Medical University of South Carolina, Charleston; and Department of Pharmacology (W.B.C., K.N.), Medical College of Wisconsin, Milwaukee.
  • Dennis L. Ball
    From the William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology of the University of Wisconsin (T.L.G., D.L.B.); Madison; Department of Medicine (B.M.E.), Medical University of South Carolina, Charleston; and Department of Pharmacology (W.B.C., K.N.), Medical College of Wisconsin, Milwaukee.
  • Brent M. Egan
    From the William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology of the University of Wisconsin (T.L.G., D.L.B.); Madison; Department of Medicine (B.M.E.), Medical University of South Carolina, Charleston; and Department of Pharmacology (W.B.C., K.N.), Medical College of Wisconsin, Milwaukee.
  • William B. Campbell
    From the William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology of the University of Wisconsin (T.L.G., D.L.B.); Madison; Department of Medicine (B.M.E.), Medical University of South Carolina, Charleston; and Department of Pharmacology (W.B.C., K.N.), Medical College of Wisconsin, Milwaukee.
  • Kasem Nithipatikom
    From the William S. Middleton Memorial Veterans Hospital and Departments of Medicine and Pharmacology of the University of Wisconsin (T.L.G., D.L.B.); Madison; Department of Medicine (B.M.E.), Medical University of South Carolina, Charleston; and Department of Pharmacology (W.B.C., K.N.), Medical College of Wisconsin, Milwaukee.

書誌事項

公開日
2004-02
DOI
  • 10.1161/01.hyp.0000113294.06704.64
公開者
Ovid Technologies (Wolters Kluwer Health)

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説明

<jats:p> Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10( <jats:italic>trans</jats:italic> )-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 μmol/L, and inhibited aldosteronogenesis at higher doses. EKODE’s stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid’s mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10 <jats:sup>−9</jats:sup> to 5×10 <jats:sup>−7</jats:sup> mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone ( <jats:italic>r</jats:italic> =0.53, <jats:italic>P</jats:italic> =0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks. </jats:p>

収録刊行物

  • Hypertension

    Hypertension 43 (2), 358-363, 2004-02

    Ovid Technologies (Wolters Kluwer Health)

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