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Low-dose renin inhibitor and low-dose AT1-receptor blocker therapy ameliorate target-organ damage in rats harbouring human renin and angiotensinogen genes

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

Erdenechimeg Shagdarsuren

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany, Novartis Institue for Biomedical Research, East Hanover, New Jersey, USA

Petra Gratze

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

Anette Fiebeler

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

Bernhard Pilz

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

Silke Meiners

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

Wolfgang Derer

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany

David L Feldman

Novartis Institue for Biomedical Research, East Hanover, New Jersey, USA

Randy Webb

Novartis Institue for Biomedical Research, East Hanover, New Jersey, USA

Dominik N Muller

Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany, dominikmueller{at}mdc-berlin.de, Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany

We studied the effects of extremely low-dose human renin inhibition (aliskiren) with low angiotensin II receptor blockade (losartan) in a novel double-transgenic rat model harbouring both human renin and angiotensinogen genes. We found that low-dose aliskiren and low-dose losartan effectively reduced mortality and target-organ damage with minimal, non-significant, effects on blood pressure (BP). Our data suggest that renin-angiotensin system (RAS) inhibition ameliorates target-organ damage in an Ang II-driven model of hypertension. Direct renin inhibition is equally efficacious in this regard. Our study does not fully answer the question of BP-lowering versus RAS inhibition. This question is important and was at least partially addressed with our low-dose model.

Key Words: angiotensin II • renin inhibitor • inflammation • albuminuria • cardiac damage

Journal of Renin-Angiotensin-Aldosterone System, Vol. 8, No. 2, 81-84 (2007)
DOI: 10.3317/jraas.2007.008


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