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, Louise M. Burrell

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    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)335-345
    Number of pages11
    JournalClinical science
    Volume120
    Issue number8
    DOIs
    StatePublished - Apr 1 2011

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    Keywords

    • Angiotensin peptide
    • Cardiac fibrosis
    • Kidney failure
    • Renal mass reduction
    • Renin-angiotensin system

    ASJC Scopus subject areas

    • Medicine(all)

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