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

• Published in: Experimental physiology 2008-05, Vol.93 (5), p.622-630
• Main Authors: Burchill, L., Velkoska, E., Dean, R. G., Lew, R. A., Smith, A. I., Levidiotis, V., Burrell, L. M.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - enzymology; Acute Kidney Injury - genetics; Acute Kidney Injury - pathology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Autoradiography; Blood Pressure - physiology; Body Weight - drug effects; Collagen - metabolism; Drinking - physiology; Fluorescent Dyes; Gene Expression Regulation, Enzymologic - physiology; Heart Function Tests; Heart Rate - physiology; Kidney Function Tests; Myocardium - enzymology; Myocardium - pathology; Nephrectomy; Peptidyl-Dipeptidase A - biosynthesis; Proteinuria - etiology; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Urodynamics - physiology; Ventricular Remodeling - physiology
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2007.040386

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.