Angiotensin I-Converting Enzyme Modulates Neutral Endopeptidase Activity in the Rat

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  • Carla Oliveri
    Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.
  • María Paz Ocaranza
    Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.
  • Ximena Campos
    Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.
  • Sergio Lavandero
    Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.
  • Jorge E. Jalil
    Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.

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Abstract

<jats:p> <jats:italic> <jats:italic>Abstract</jats:italic> — </jats:italic> — Angiotensin I is a substrate for both ACE and for neutral endopeptidase 24.11 (NEP). We hypothesized that high ACE expression is related to low NEP activity. Accordingly, circulating and tissue NEP and ACE activities were measured by fluorometry in homozygous rats (F <jats:sub>0</jats:sub> and F <jats:sub>2</jats:sub> ) for the Lewis microsatellite allele (LL, low ACE) and for the Brown Norway microsatellite allele (BB, high ACE). Plasma, lung, and aortic ACE activities in F <jats:sub>0</jats:sub> and F <jats:sub>2</jats:sub> were higher in BB rats than in LL rats ( <jats:italic>P</jats:italic> <0.01), whereas left ventricular ACE activity was similar in both genotypes. In contrast, NEP activity in the LL group was higher in the serum, aorta, and lungs in F <jats:sub>0</jats:sub> and F <jats:sub>2</jats:sub> homozygous ( <jats:italic>P</jats:italic> <0.05). Plasma ACE activity was inversely correlated with serum ( <jats:italic>r</jats:italic> =−0.6 and −0.598 in F <jats:sub>0</jats:sub> and F <jats:sub>2</jats:sub> , respectively; <jats:italic>P</jats:italic> <0.03) and lung NEP activities ( <jats:italic>r</jats:italic> =−0.77 in F <jats:sub>0</jats:sub> and <jats:italic>r</jats:italic> =−0.59 in F <jats:sub>2</jats:sub> , <jats:italic>P</jats:italic> <0.01). Aortic ACE and NEP activities were also correlated ( <jats:italic>r</jats:italic> =−0.696 and −0.584 in F <jats:sub>0</jats:sub> and F <jats:sub>2</jats:sub> , respectively; <jats:italic>P</jats:italic> <0.03). In conclusion, genetically determined high ACE expression in rats is inversely related to tissue NEP activity, which could determine lower angiotensin-(1-7) tissue levels. </jats:p>

Journal

  • Hypertension

    Hypertension 38 (3), 650-654, 2001-09

    Ovid Technologies (Wolters Kluwer Health)

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