title: Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.
abstract: We previously reported that exogenous angiotensin (Ang) 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE) activity. This study investigated if the addition of an ACE inhibitor (ACEi) to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx) and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day), Ang 1-7 (subcutaneous 24 μg/kg/h) or dual therapy (all groups, n = 12). A control group (n = 10) of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gayed
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Griggs
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Sheila K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Elena
authors.identifier: http://orcid.org/0000-0002-7946-0944
authors.initials: E
authors.lastname: Velkoska
mesh_terms: D000704:Analysis of Variance; D000803:Angiotensin I; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009392:Nephrectomy; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7); D017257:Ramipril