Document Detail


Beneficial cardiac effects of the renin inhibitor aliskiren in spontaneously hypertensive rats.
MedLine Citation:
PMID:  20625318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The blood pressure-lowering effect of the renin inhibitor aliskiren equals that of angiotensin-converting enzyme (ACE) inhibitors and angiotensin (Ang) II type 1 (AT1) receptor blockers. Whether aliskiren offers end-organ protection remains to be investigated. Here, we compared the cardiac effects of aliskiren, the AT1 receptor blocker irbesartan and the ACE inhibitor captopril in spontaneously hypertensive rats (SHR) at equi-hypotensive doses.
METHODS AND RESULTS: SHR were treated for 1-3 weeks with vehicle, aliskiren, captopril or irbesartan (100, 3 and 15 mg/kg per day, respectively) using an osmotic minipump, and compared to vehicle-treated Wistar-Kyoto (WKY) controls. All drugs lowered (but not normalized) mean arterial pressure in SHR equi-effectively, as monitored by radiotelemetry, without altering heart rate. All drugs also reduced the increased cardiomyocyte area in SHR, and tended to normalize the elevated brain natriuretic peptide plasma levels. In the Langendorff set-up, all drugs normalized the diminished endothelium-dependent vasodilator response to bradykinin in SHR. Moreover, aliskiren and irbesartan, but not captopril, decreased the enhanced coronary Ang II response in SHR. Aliskiren reduced plasma renin activity and the plasma and tissue angiotensin levels at 1 week of treatment; yet, after 3 weeks of aliskiren treatment only the cardiac angiotensin levels remained suppressed, whereas no tissue angiotensin reductions were seen with captopril or irbesartan.
CONCLUSION: For a given decrease in blood pressure, aliskiren improves coronary endothelial function and decreases cardiac hypertrophy in SHR to at least the same degree as ACE inhibition and AT1 receptor blockade. In addition, aliskiren diminishes the enhanced Ang II response in the coronary circulation of SHR and offers superior long-term cardiac angiotensin suppression.
Authors:
Joep H M van Esch; Els Moltzer; Richard van Veghel; Ingrid M Garrelds; Frank Leijten; Angelique M Bouhuizen; A H Jan Danser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-16     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  2145-55     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Amides / pharmacology*,  therapeutic use
Angiotensin II Type 1 Receptor Blockers / pharmacology
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Angiotensins / blood
Animals
Biphenyl Compounds / pharmacology
Blood Pressure / drug effects*,  physiology
Captopril / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Fumarates / pharmacology*,  therapeutic use
Heart / drug effects*,  physiopathology
Heart Ventricles / pathology
Hypertension / blood,  drug therapy,  physiopathology*
Hypertrophy / drug therapy
Male
Natriuretic Peptide, Brain / blood
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Renin / antagonists & inhibitors*,  blood
Tetrazoles / pharmacology
Chemical
Reg. No./Substance:
0/Amides; 0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Angiotensins; 0/Biphenyl Compounds; 0/Fumarates; 0/Tetrazoles; 0/aliskiren; 114471-18-0/Natriuretic Peptide, Brain; 138402-11-6/irbesartan; 62571-86-2/Captopril; EC 3.4.23.15/Renin

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