Published Online
on October 27, 2008

A more recent version of this article appeared on December 1, 2008

This Article Full Text (PDF) Data Supplement All Versions of this Article: 52/6/1068    most recent HYPERTENSIONAHA.108.116350v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Westermann, D. Articles by Tschöpe, C. Search for Related Content PubMed PubMed Citation Articles by Westermann, D. Articles by Tschöpe, C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Heart Attack Related Collections Structure Contractile function Congestive ACE/Angiotension receptors Animal models of human disease Hypertrophy Acute myocardial infarction Related Article

Submitted on May 14, 2008
Revised on June 14, 2008

Renin Inhibition Improves Cardiac Function and Remodeling After Myocardial Infarction Independent of Blood Pressure

Dirk Westermann^*; Alexander Riad; Olga Lettau; Anton Roks; Konstantinos Savvatis; Peter Moritz Becher; Felicitas Escher; A. H. Jan Danser; Heinz-Peter Schultheiss; and Carsten Tschöpe^*

From the Department of Cardiology and Pneumology (D.W., A.R., O.L., K.S., P.M.B., F.E., H.-P.S., C.T.), Campus Benjamin Franklin, Charité–Universitätsmedizin Berlin, Berlin, Germany; and the Division of Vascular Pharmacology and Metabolism (A.R., A.H.J.D.), Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.

^* To whom correspondence should be addressed. E-mail: dirk.westermann{at}web.de or ctschoepe{at}yahoo.com.

Abstract—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.

Key words: aliskiren • renin inhibitor • myocardial infarction • cardiac remodeling • matrix metalloproteinase

Related Article:

Direct Renin Inhibition: Another Weapon to Modulate the Renin-Angiotensin System in Postinfarction Remodeling?

Stefano Perlini, Francesco Salinaro, and Maria Luisa Fonte
Hypertension 2008 52: 1019-1021. [Extract] [Full Text] [PDF]

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