HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 93/5/622    most recent expphysiol.2007.040386v1 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 Citing Articles Citing Articles via HighWire Google Scholar Articles by Burchill, L. Articles by Burrell, L. M. PubMed PubMed Citation Articles by Burchill, L. Articles by Burrell, L. M. Related Collections Genomic Physiology

¹ Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia ² Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia ³ Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Camperdown, Sydney, NSW, Australia

Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin-converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague–Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n = 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg^–1 day^–1 (n = 15) or vehicle (n = 13) orally for 10 days after surgery. Rats with AKI had polyuria (P < 0.001), proteinuria (P < 0.001) and hypertension (P < 0.001). Cardiac structural changes were present and characterized by LVH (P < 0.001), fibrosis (P < 0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P < 0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P < 0.01) and ACE2 activity (P < 0.05). Ramipril decreased blood pressure (P < 0.001), LVH (P < 0.001), fibrosis (P < 0.01) and BNP mRNA (P < 0.01). These changes occurred in association with inhibition of cardiac ACE (P < 0.05) and a reduction in cardiac ACE2 activity (P < 0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin-converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1–7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity.

(Received 29 November 2007; accepted after revision 25 January 2008; first published online 25 January 2008)
Corresponding author L. M. Burrell: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia. Email: l.burrell{at}unimelb.edu.au

This article has been cited by other articles:

				M. K. Raizada and J. F. R. Paton Recent advances in the renin-angiotensin system: angiotensin-converting enzyme 2 and (pro)renin receptor Exp Physiol, May 1, 2008; 93(5): 517 - 518. [Full Text] [PDF]