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Title: Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition
Austin Authors: Burrell, Louise M ;Gayed, Daniel;Griggs, Karen;Patel, Sheila K ;Velkoska, Elena
Affiliation: Medicine (University of Melbourne)
Issue Date: 27-Feb-2017
Date: 2017-02-27
Publication information: PLoS One 2017; 12(2): e0171975
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.
DOI: 10.1371/journal.pone.0171975
ORCID: 0000-0003-1863-7539
Journal: PLoS One
PubMed URL:
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
Appears in Collections:Journal articles

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