Document Detail


Direct renin inhibition: an update.
MedLine Citation:
PMID:  19895758     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action. When combined with agents that inhibit the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers, additional blood pressure reduction reflects more complete RAAS blockade. Concern that marked elevation in plasma renin concentration following aliskiren administration might lead to RAAS-induced paradoxical blood pressure increases appears unfounded, based upon analyses of patients participating in clinical trials. Studies in animals and humans indicate that aliskiren accumulates in renal tissue, blocks the intrarenal RAAS, and interferes with deleterious cellular effects of angiotensin II by mechanisms that may include enzymatic blockade of renin and prorenin at the site of the (pro)renin receptor. In patients with diabetic nephropathy, adding aliskiren to losartan resulted in an additional 20% reduction in urinary protein excretion. In patients with heart failure, aliskiren reduced brain natriuretic peptide levels when added to other RAAS inhibitors, suggesting an additional hemodynamic effect. The ASPIRE HIGHER clinical trials program is assessing whether the promising pharmacologic properties of aliskiren translate into long-term clinical benefits.
Authors:
Rekha Pinto; Alan H Gradman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current hypertension reports     Volume:  11     ISSN:  1534-3111     ISO Abbreviation:  Curr. Hypertens. Rep.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888982     Medline TA:  Curr Hypertens Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  456-62     Citation Subset:  IM    
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