Effects of Aliskiren on Blood Pressure, Albuminuria, and (Pro)Renin Receptor Expression in Diabetic TG(mRen-2)27 Rats

DOI Web Site 被引用文献17件
  • David L. Feldman
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Liang Jin
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Hong Xuan
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Aurelie Contrepas
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Yinong Zhou
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Randy L. Webb
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Dominik N. Mueller
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Sandra Feldt
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Frederick Cumin
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Wieslawa Maniara
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Elke Persohn
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Helmut Schuetz
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • A.H. Jan Danser
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.
  • Genevieve Nguyen
    From Novartis Institutes for Biomedical Research (D.L.F., L.J., H.X., Y.Z., R.L.W., F.C., W.M.), E. Hanover, NJ and Cambridge, Mass; Inserm Unit 833 (A.C., G.N.), Paris, France; Chaire de Médecine Expérimentale (A.C., G.N.), Collège de France, Paris, France; Max-Delbruck-Center (D.N.M., S.F.), Berlin-Buch, Germany; Novartis Pharma AG (E.P., H.S.), Basel, Switzerland; and the Department of Pharmacology (A.H.J.D.), Erasmus MC, Rotterdam, The Netherlands.

書誌事項

公開日
2008-07
DOI
  • 10.1161/hypertensionaha.107.108845
公開者
Ovid Technologies (Wolters Kluwer Health)

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説明

<jats:p> The aim of this study was to explore the effects of the renin inhibitor aliskiren in streptozotocin-diabetic TG(mRen-2)27 rats. Furthermore, we investigated in vitro the effect of aliskiren on the interactions between renin and the (pro)renin receptor and between aliskiren and prorenin. Aliskiren distributed extensively to the kidneys of normotensive (non)diabetic rats, localizing in the glomeruli and vessel walls after 2 hours exposure. In diabetic TG(mRen-2)27 rats, aliskiren (10 or 30 mg/kg per day, 10 weeks) lowered blood pressure, prevented albuminuria, and suppressed renal transforming growth factor-β and collagen I expression versus vehicle. Aliskiren reduced (pro)renin receptor expression in glomeruli, tubules, and cortical vessels compared to vehicle (in situ hybridization). In human mesangial cells, aliskiren (0.1 μmol/L to 10 μmol/L) did not inhibit binding of <jats:sup>125</jats:sup> I-renin to the (pro)renin receptor, nor did it alter the activation of extracellular signal-regulated kinase 1/2 by renin (20 nmol/L) preincubated with aliskiren (100 nmol/L) or affect gene expression of the (pro)renin receptor. Evidence was obtained that aliskiren binds to the active site of prorenin. The above results demonstrate the antihypertensive and renoprotective effects of aliskiren in experimental diabetic nephropathy. The evidence that aliskiren can reduce in vivo gene expression for the (pro)renin receptor and that it may block prorenin-induced angiotensin generation supports the need for additional work to reveal the mechanism of the observed renoprotection by this renin inhibitor. </jats:p>

収録刊行物

  • Hypertension

    Hypertension 52 (1), 130-136, 2008-07

    Ovid Technologies (Wolters Kluwer Health)

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