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

Exp Physiol. 2008 May;93(5):622-30. doi: 10.1113/expphysiol.2007.040386. Epub 2008 Jan 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / enzymology*
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / pathology*
  • Angiotensin-Converting Enzyme 2
  • 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
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urodynamics / physiology
  • Ventricular Remodeling / physiology*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Fluorescent Dyes
  • RNA, Messenger
  • Collagen
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2