gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Aliskiren, a human renin inhibitor, reverses cardiac and renal damage in double-transgenic rats

Meeting Abstract (Hypertonie 2004)

  • B. Pilz - HELIOS Klinikum-Berlin, Franz Volhard Clinic and Medical Faculty of the Charité, Humboldt University of Berlin (Berlin, D)
  • E. Shagdarsuren - HELIOS Klinikum-Berlin, Franz Volhard Clinic and Medical Faculty of the Charité, Humboldt University of Berlin (Berlin, D)
  • M. Wellner - HELIOS Klinikum-Berlin, Franz Volhard Clinic and Medical Faculty of the Charité, Humboldt University of Berlin (Berlin, D)
  • A. Fiebeler - HELIOS Klinikum-Berlin, Franz Volhard Clinic and Medical Faculty of the Charité, Humboldt University of Berlin (Berlin, D)
  • R. Dechend - HELIOS Klinikum-Berlin, Franz Volhard Clinic and Medical Faculty of the Charité, Humboldt University of Berlin (Berlin, D)
  • P. Gratze - Max-Delbrück-Center for Molecular Medicine (Berlin-Buch, D)
  • S. Meiners - Max-Delbrück-Center for Molecular Medicine (Berlin-Buch, D)
  • D. Feldman - Max-Delbrück-Center for Molecular Medicine (Berlin-Buch, D)
  • R. Webb - Max-Delbrück-Center for Molecular Medicine (Berlin-Buch, D)
  • F. Luft - Novartis Pharmaceuticals, East Hanover, New Jersey, USA
  • D. Müller - Novartis Pharmaceuticals, East Hanover, New Jersey, USA

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP63

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch063.shtml

Veröffentlicht: 10. August 2005

© 2005 Pilz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

We tested the hypothesis that Aliskiren reverses organ damage in rats transgenic for human renin and angiotensinogen genes (dTGR). Six week-old dTGR were matched by albuminuria (2 mg/d) and divided in 5 groups. Untreated dTGR were compared with Aliskiren (3 and 0.3mg/kg/d by mini pumps) and valsartan (Val 10 and 1 mg/kg/d in the diet). Treatment was week 6 through 9. At week 6, all groups had elevated systolic blood pressure (BP). Aliskiren promptly lowered BP (115±6 and 139±5 mm Hg; p<0.05) and albuminuria (0.4±0.1 and 1.6±0.6 mg/d; p<0.05) at both doses. Untreated dTGR showed increased BP (202±4 mm Hg) and albuminuria (34±5.7 mg/d) at week 7. While high dose Val lowered BP (148±4 mm Hg) and albuminuria (2.1±0.7 mg/d) similarly compared to Aliskiren (0.3mg/kg/d), low dose Val reduced BP (182±3 mm Hg) and albuminuria (24±3.8 mg/d) slightly. By week 9, 100% (19/19) untreated dTGR died, whereas only 26% (5/19) of the Val (1 mg/kg/d), and no rat in the other groups died. At week 9, low dose Val barely kept dTGR alive. The rats had cardiac hypertrophy (4.4±0.1 mg/g), increased left ventricular (LV) wall thickness, signs of diastolic dysfunction (E<A), increased LV atrial natriuretic peptide, and b-myosin heavy chain mRNA expression, reduced a-myosin heavy chain mRNA expression, albuminuria (24±4 mg/d), renal and cardiac fibrosis, and inflammatory cell infiltration in kidney and heart. In contrast, both Aliskiren doses and high-dose Val lowered BP, albuminuria, cardiac, and renal damage. Direct renin inhibition offers an attractive alternative in reversing Ang II-induced organ damage.