Document Detail


Direct inhibition of renin as a cardiovascular pharmacotherapy: focus on aliskiren.
MedLine Citation:
PMID:  17700383     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The important role of renin-angiotensin-aldosterone system blockade in the treatment of systemic hypertension, heart failure, diabetic kidney disease, and atherogenesis has been clearly established. The theoretical therapeutic advantages for inhibiting the detrimental effects of the renin-angiotensin system at its most upstream point have served as the impetus for the development of renin inhibitors. The advent of aliskiren, the first in a novel class of orally active, nonpeptide, highly specific, human renin inhibitors, provides a new modality in the armamentarium of renin-angiotensin system antagonists. Studies in marmosets and rats demonstrated that aliskiren reduced blood pressure in a dose-dependent manner and is highly efficacious in blocking plasma renin activity with parallel reductions in the levels of the other downstream constituents of the renin-angiotensin system. Clinical trials in hypertensive patients have confirmed these benefits with aliskiren whose blood pressure-lowering efficacy is similar to or better than those of standard therapeutic doses of enalapril, losartan, irbesartan, and hydrochlorothiazide. Aliskiren is well tolerated, with few reported adverse effects even at the highest doses tested. Given the established beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the treatment of cardiovascular and renovascular diseases, future studies may further elucidate a similar protective role for aliskiren both as a monotherapy and as part of a combination therapy.
Authors:
Reza Sepehrdad; William H Frishman; Charles T Stier; Domenic A Sica
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Cardiology in review     Volume:  15     ISSN:  1538-4683     ISO Abbreviation:  Cardiol Rev     Publication Date:    2007 Sep-Oct
Date Detail:
Created Date:  2007-08-16     Completed Date:  2007-09-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9304686     Medline TA:  Cardiol Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  242-56     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, UC Davis Medical Center, Sacramento, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / blood
Amides / adverse effects,  chemistry,  pharmacokinetics,  pharmacology,  therapeutic use*
Angiotensin II / blood,  physiology
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Animals
Antihypertensive Agents / adverse effects,  pharmacology*,  therapeutic use
Biphenyl Compounds / pharmacology,  therapeutic use
Blood Pressure / drug effects,  physiology
Fumarates / adverse effects,  chemistry,  pharmacokinetics,  pharmacology,  therapeutic use*
Humans
Kidney / blood supply
Piperazines / pharmacology,  therapeutic use
Randomized Controlled Trials as Topic
Receptors, Angiotensin / drug effects,  physiology
Regional Blood Flow
Renin / antagonists & inhibitors*,  physiology
Renin-Angiotensin System / drug effects,  physiology
Structure-Activity Relationship
Tetrazoles / pharmacology,  therapeutic use
Thiazoles / pharmacology,  therapeutic use
Chemical
Reg. No./Substance:
0/Amides; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Biphenyl Compounds; 0/Fumarates; 0/Piperazines; 0/Receptors, Angiotensin; 0/Tetrazoles; 0/Thiazoles; 0/aliskiren; 11128-99-7/Angiotensin II; 138402-11-6/irbesartan; 138742-43-5/zankiren hydrochloride; 52-39-1/Aldosterone; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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