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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 2011
Externally publishedYes

Fingerprint

Nephrectomy
Blood Pressure
Cardiomegaly
Peptidyl-Dipeptidase A
Ramipril
Kidney
Fibrosis
angiotensin I (1-7)
Kidney Diseases
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
Renal Insufficiency
Sprague Dawley Rats
Control Groups
Peptides

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy. / Velkoska, Elena; Dean, Rachael G.; Griggs, Karen; Burchill, Luke; Burrell, Louise M.

In: Clinical Science, Vol. 120, No. 8, 04.2011, p. 335-345.

Research output: Contribution to journalArticle

Velkoska, Elena ; Dean, Rachael G. ; Griggs, Karen ; Burchill, Luke ; Burrell, Louise M. / Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy. In: Clinical Science. 2011 ; Vol. 120, No. 8. pp. 335-345.
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