title: End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899.
abstract: OBJECTIVE
  To compare the therapeutic efficacy of SAR407899 with the current standard treatment for hypertension [an angiotensin converting enzyme (ACE)-inhibitor and a calcium channel blocker] and compare the frequency and severity of the hypertension-related end-organ damage.
  
  
  METHODS
  Long-term pharmacological characte-rization of SAR407899 has been performed in two animal models of hypertension, of which one is sensitive to ACE-inhibition (LNAME) and the other is insensitive [deoxycorticosterone acetate (DOCA)]. SAR407899 efficiently lowered high blood pressure and significantly reduced late-stage end organ damage as indicated by improved heart, kidney and endothelial function and reduced heart and kidney fibrosis in both models of chronic hypertension.
  
  
  RESULTS
  Long term treatment with SAR407899 has been well tolerated and dose-dependently reduced elevated blood pressure in both models with no signs of tachyphylaxia. Blood pressure lowering effects and protective effects on hypertension related end organ damage of SAR407899 were superior to ramipril and amlodipine in the DOCA rat. Typical end-organ damage was significantly reduced in the SAR407899-treated animals. Chronic administration of SAR407899 significantly reduced albuminuria in both models. The beneficial effect of SAR407899 was associated with a reduction in leukocyte/macrophage tissue infiltration. The overall protective effect of SAR407899 was superior or comparable to that of ACE-inhibition or calcium channel blockade. Chronic application of SAR407899 protects against hypertension and hypertension-induced end organ damage, regardless of the pathophysiological mechanism of hypertension.
  
  
  CONCLUSIONS
  Rho-kinases-inhibition by the SAR407899 represents a new therapeutic option for the treatment of hypertension and its complications.
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Matthias
authors: M
authors: Löhn
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Oliver
authors: O
authors: Plettenburg
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Aimo
authors: A
authors: Kannt
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Markus
authors: M
authors: Kohlmann
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Armin
authors: A
authors: Hofmeister
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Dieter
authors: D
authors: Kadereit
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Peter
authors: P
authors: Monecke
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Alexander
authors: A
authors: Schiffer
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Anke
authors: A
authors: Schulte
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Hartmut
authors: H
authors: Ruetten
authors: Matthias Löhn, Oliver Plettenburg, Aimo Kannt, Markus Kohlmann, Armin Hofmeister, Dieter Kadereit, Peter Monecke, Alexander Schiffer, Anke Schulte, Hartmut Ruetten, Yuri Ivashchenko, Translational Medicine, Sanofi-Aventis, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors: Yuri
authors: Y
authors: Ivashchenko
keywords: Angiotensin converting enzyme-inhibition; End organ damage; Hypertension; Rho-kinase
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