title: Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy.
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.
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Velkoska
authors.forename: Rachael G
authors.initials: RG
authors.lastname: Dean
authors.forename: Karen
authors.initials: K
authors.lastname: Griggs
authors.forename: Luke
authors.initials: L
authors.lastname: Burchill
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
mesh_terms: D000803:Angiotensin I / Q000633:toxicity*; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use / Q000633:toxicity*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D009392:Nephrectomy; D010446:Peptide Fragments / Q000633:toxicity*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017257:Ramipril / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000150:complications* / Q000201:enzymology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D017257:Ramipril