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Clinical Science (2011) 120, (335–345) (Printed in Great Britain)

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Angiotensin-(1–7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy

Elena Velkoska, Rachael G. Dean, Karen Griggs, Luke Burchill and Louise M. Burrell

Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia

Key words: angiotensin peptide, cardiac fibrosis, kidney failure, renal mass reduction, renin–angiotensin system.

Abbreviations: ACE, angiotensin-converting enzyme; Ang, angiotensin; AT₁R etc., angiotensin type 1 receptor etc.; BNP, brain natriuretic peptide; EMT, epithelial-to-mesenchymal transition; LV, left ventricle; LVEDP, left ventricular end-diastolic pressure; KO, knockout; PRA, plasma renin activity; QFS, quenched fluorescent substrate; qRT, quantitative real-time; RAS, renin–angiotensin system; SD, Sprague–Dawley; STNx, subtotal nephrectomy; TGF-β1, transforming growth factor-β1; 2K1C, two-kidney/one-clip.

Correspondence: Professor Louise Burrell (email l.burrell@unimelb.edu.au).

ACE (angiotensin-converting enzyme) 2 is expressed in the heart and kidney and metabolizes Ang (angiotensin) II to Ang-(1–7) a peptide that acts via the Ang-(1–7) or mas receptor. The aim of the present study was to assess the effect of Ang-(1–7) on blood pressure and cardiac remodelling in a rat model of renal mass ablation. Male SD (Sprague–Dawley) rats underwent STNx (subtotal nephrectomy) and were treated for 10 days with vehicle, the ACE inhibitor ramipril (oral 1 mg·kg⁻¹ of body weight·day⁻¹) or Ang-(1–7) (subcutaneous 24 μg·kg⁻¹ of body weight·h⁻¹) (all n = 15 per group). A control group (n = 10) of sham-operated rats were also studied. STNx rats were hypertensive (P<0.01) with renal impairment (P<0.001), cardiac hypertrophy (P<0.001) and fibrosis (P<0.05), and increased cardiac ACE (P<0.001) and ACE2 activity (P<0.05). Ramipril reduced blood pressure (P<0.01), improved cardiac hypertrophy (P<0.001) and inhibited cardiac ACE (P<0.001). By contrast, Ang-(1–7) infusion in STNx was associated with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05) and fibrosis (P<0.01). Ang-(1–7) infusion also increased cardiac ACE activity (P<0.001) and reduced cardiac ACE2 activity (P<0.05) compared with STNx-vehicle rats. Our results add to the increasing evidence that Ang-(1–7) may have deleterious cardiovascular effects in kidney failure and highlight the need for further in vivo studies of the ACE2/Ang-(1–7)/mas receptor axis in kidney disease.

Received 1 June 2010/17 November 2010; accepted 19 November 2010

Published as Immediate Publication 19 November 2010, doi:10.1042/CS20100280

© 2011 The Author(s)
The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.