RGD Reference Report - Reduction in renal ACE2 expression in subtotal nephrectomy is ameliorated with ACE inhibition. - Rat Genome Database

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Reduction in renal ACE2 expression in subtotal nephrectomy is ameliorated with ACE inhibition.

Authors: Velkoska, E  Dean, RG  Burchill, LJ  Levidiotis, V  Burrell, LM 
Citation: Velkoska E, etal., Clin Sci (Lond). 2009 Aug 21.
RGD ID: 2314413
Pubmed: PMID:19698082   (View Abstract at PubMed)
PMCID: PMC2782317   (View Article at PubMed Central)
DOI: DOI:10.1042/CS20090318   (Journal Full-text)

Alterations within the renin-angiotensin system (RAS) are pivotal for the development of renal disease. Angiotensin-converting enzyme (ACE) 2 is expressed in the kidney, and converts the vasoconstrictor angiotensin (Ang) II to Ang 1-7, a peptide with vasodilatory and anti-fibrotic actions. Whilst the expression of ACE2 in the diabetic kidney has been well studied, little is known about its expression in non-diabetic renal disease. We assessed ACE2 in rats with acute kidney injury induced by subtotal nephrectomy (STNx). STNx and Control rats received vehicle or ramipril (1 mg/kg/d), and measured renal ACE, ACE2 and mas receptor gene and protein expression 10 days later. STNx rats were characterised by polyuria, proteinuria, hypertension and elevated plasma ACE2 activity (all P<0.01), and plasma Ang 1-7 (P<0.05) compared to Control. There was increased cortical ACE binding and medullary mas receptor expression (P<0.05), but reduced cortical and medullary ACE2 activity in the remnant kidney (P<0.05, P<0.001) compared to Control. In STNx, ramipril reduced blood pressure (P<0.01), polyuria (P<0.05) and plasma ACE2 (P<0.01), increased plasma Ang 1-7 (P<0.001), and inhibited renal ACE (P<0.001). Ramipril increased both cortical and medullary ACE2 activity (P<0.01) but reduced medullary mas receptor expression (P<0.05). Our results show that ACE2 activity is reduced in kidney injury, and that ACE inhibition produced beneficial effects in association with increased renal ACE2 activity. As ACE2 both degrades Ang II and generates the vasodilator, Ang 1-7, a decrease in renal ACE2 activity as observed in this study has the potential to contribute to the progression of kidney disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 2314413ramiprilRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mas1  (MAS1 proto-oncogene, G protein-coupled receptor)


Additional Information