Received November 29, 2007
Revised January 2, 2008
Accepted after revision January 25, 2008
ACE2 and renal failure Acute kidney injury in the rat causes cardiac remodelling and increases ACE2 expression
Luke Burchill 1,
Elena Velkoska 1,
Rachael G Dean 1,
Rebecca A Lew 2,
A. Ian Smith 2,
Vicki Levidiotis 3,
Louise Burrell 1*
1 University of Melbourne
2 Monash University
3 University of Sydney
* To whom correspondence should be addressed. E-mail: l.burrell{at}unimelb.edu.au.
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Abstract |
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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 if 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 (STNx) surgery. Control rats received vehicle (N=10), and STNx rats received the ACE inhibitor (ACEi), ramipril, 1 mg/kg/day (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 characterised by left ventricular hypertrophy (LVH) (P<0.001), fibrosis (P<0.001), and increased cardiac 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 characterised by hypertrophy, fibrosis and increased cardiac ACE2. ACE2 by promoting the production of the antifibrotic peptide, Ang 1-7 may have a cardioprotective role in AKI, particularly as amelioration of adverse cardiac effects with ACE inhibition was associated with normalisation of cardiac ACE2 activity.
Key Words:
Angiotensin, Heart, Kidney
