Document Detail

Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure.
MedLine Citation:
PMID:  18955663     Owner:  NLM     Status:  MEDLINE    
Pharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac remodeling, apoptosis, and left ventricular (LV) function after experimental myocardial infarction (MI). C57J/bl6 mice were subjected to coronary artery ligation and were treated for 10 days with vehicle or aliskiren (50 mg/kg per day via an SC osmopump), whereas sham-operated animals served as controls. This dose of aliskiren, which did not affect systemic blood pressure, improved systolic and diastolic LV function, as measured by the assessment of pressure-volume loops after MI. Furthermore, after MI LV dilatation, cardiac hypertrophy and lung weights were decreased in mice treated with aliskiren compared with placebo-treated mice after MI. This was associated with a normalization of the mitogen-activated protein kinase P38 and extracellular signal-regulated kinases 1/2, AKT, and the apoptotic markers bax and bcl-2 (all measured by Western blots), as well as the number of TUNEL-positive cells in histology. LV dilatation, as well as the associated upregulation of gene expression (mRNA abundance) and activity (by zymography) of the cardiac metalloproteinase 9 in the placebo group after MI, was also attenuated in the aliskiren-treated group. Aliskiren improved LV dysfunction after MI in a dose that did not affect blood pressure. This was associated with the amelioration of cardiac remodelling, hypertrophy, and apoptosis.
Dirk Westermann; Alexander Riad; Olga Lettau; Anton Roks; Konstantinos Savvatis; Peter Moritz Becher; Felicitas Escher; A H Jan Danser; Heinz-Peter Schultheiss; Carsten Tschöpe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-27
Journal Detail:
Title:  Hypertension     Volume:  52     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2008-12-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1068-75     Citation Subset:  IM    
Department of Cardiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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MeSH Terms
Amides / pharmacology*
Antihypertensive Agents / pharmacology*
Apoptosis / drug effects
Blood Pressure / drug effects
Cardiomegaly / complications,  drug therapy,  pathology
Collagen / genetics,  metabolism
Extracellular Matrix / enzymology
Fumarates / pharmacology*
Hypertension, Renal / complications,  drug therapy*
Matrix Metalloproteinase 9 / genetics,  metabolism
Mice, Inbred C57BL
Myocardial Infarction / complications,  drug therapy*,  pathology
Myocardium / metabolism
RNA, Messenger / metabolism
Renin / antagonists & inhibitors*,  metabolism
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Ventricular Function, Left / drug effects
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Amides; 0/Antihypertensive Agents; 0/Fumarates; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 0/aliskiren; 9007-34-5/Collagen; EC; EC Metalloproteinase 9
Comment In:
Hypertension. 2008 Dec;52(6):1019-21   [PMID:  18955659 ]

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