Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression

Luke Burchill, E. Velkoska, R. G. Dean, R. A. Lew, A. I. Smith, V. Levidiotis, L. M. Burrell

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)622-630
Number of pages9
JournalExperimental Physiology
Volume93
Issue number5
DOIs
Publication statusPublished - May 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology

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Burchill, L., Velkoska, E., Dean, R. G., Lew, R. A., Smith, A. I., Levidiotis, V., & Burrell, L. M. (2008). Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. Experimental Physiology, 93(5), 622-630. https://doi.org/10.1113/expphysiol.2007.040386