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 language | English (US) |
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Pages (from-to) | 335-345 |
Number of pages | 11 |
Journal | Clinical science |
Volume | 120 |
Issue number | 8 |
DOIs | |
State | Published - Apr 2011 |
Externally published | Yes |
Keywords
- Angiotensin peptide
- Cardiac fibrosis
- Kidney failure
- Renal mass reduction
- Renin-angiotensin system
ASJC Scopus subject areas
- General Medicine