Low-dose renin inhibitor and low-dose AT(1)-receptor blocker therapy ameliorate target-organ damage in rats harbouring human renin and angiotensinogen genes.
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.
Dechend
Ralf
R
Universitary Medicine Berlin, Charite Campus Buch, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Germany.
Shagdarsuren
Erdenechimeg
E
Gratze
Petra
P
Fiebeler
Anette
A
Pilz
Bernhard
B
Meiners
Silke
S
Derer
Wolfgang
W
Feldman
David L
DL
Webb
Randy
R
Muller
Dominik N
DN
D000577:Amides / Q000494:pharmacology*; D000808:Angiotensinogen / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology*; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000187:drug effects / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; C446481:aliskiren; D012083:Renin