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Title: Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy.
Austin Authors: Velkoska, Elena;Dean, Rachael G;Griggs, Karen;Burchill, Luke J;Burrell, Louise M 
Affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia
Issue Date: 1-Apr-2011
Publication information: Clinical Science2011; 120(8): 335-45
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.
Gov't Doc #: 21091432
DOI: 10.1042/CS20100280
Type: Journal Article
Subjects: Angiotensin I.toxicity
Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Antihypertensive Agents.therapeutic use.toxicity
Cardiomegaly.chemically induced.drug therapy.enzymology
Disease Models, Animal
Drug Evaluation, Preclinical.methods
Hypertension.chemically induced.drug therapy.enzymology
Peptide Fragments.toxicity
Peptidyl-Dipeptidase A.metabolism
Ramipril.therapeutic use
Rats, Sprague-Dawley
Renal Insufficiency.complications.enzymology
Appears in Collections:Journal articles

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