Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11407
Title: Chronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition.
Authors: Burrell, Louise M;Burchill, Luke J;Dean, Rachael G;Griggs, Karen;Patel, Sheila K;Velkoska, Elena
Affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. l.burrell@unimelb.edu.au
Issue Date: 23-Dec-2011
Citation: Experimental Physiology 2011; 97(4): 477-85
Abstract: Renin-angiotensin system blockade slows but does not prevent the cardiovascular complications of chronic kidney disease (CKD). Angiotensin-converting enzyme (ACE) 2 is differentially regulated in acute kidney injury, with increased cardiac ACE2 but decreased kidney ACE2 levels. This study investigated the effect of long-term ACE inhibition on cardiac and renal ACE2 in rats with CKD induced by subtotal nephrectomy (STNx). Sprague-Dawley rats had sham (control) or STNx surgery. Control rats received vehicle (n = 9) and STNx rats ramipril (1 mg kg(-1) day(-1); n = 10) or vehicle (n = 10) for 28 days. Subtotal nephrectomy resulted in impaired creatinine clearance (P < 0.05), proteinuria (P < 0.05), renal fibrosis (P < 0.05) and reduced renal cortical ACE2 mRNA (P < 0.05) and activity (P < 0.05). In rats with CKD, ramipril improved creatinine clearance (P < 0.05) and was associated with an increase in cortical but not medullary ACE2 activity (P < 0.05). Compared with control rats, STNx rats were hypertensive (P < 0.01), with increased left ventricular end-diastolic pressure (LVEDP; P < 0.01), left ventricular hypertrophy (LVH; P < 0.05) and interstitial (P < 0.05) and perivascular fibrosis (P < 0.01). In rats with CKD, ramipril decreased blood pressure (P < 0.001) and reduced LVEDP (P < 0.01), LVH (P < 0.01) and perivascular fibrosis (P < 0.05) but did not significantly reduce interstitial fibrosis. There was no change in cardiac ACE2 in rats with CKD compared with control rats. In rats with CKD, ACE inhibition had major benefits to reduce blood pressure and cardiac hypertrophy and to improve creatinine clearance, but did not significantly impact on cardiac ACE2, cardiac interstitial fibrosis, renal fibrosis or proteinuria. Thus, in rats with CKD, renal ACE2 deficiency and lack of activation of cardiac ACE2 may contribute to the progression of cardiac and renal tissue injury. As long-term ACE inhibition only partly ameliorated the adverse cardio-renal effects of CKD, adjunctive therapies that lead to further increases in ACE2 activity may be needed to combat the cardio-renal complications of CKD.
Internal ID Number: 22198016
URI: http://ahro.austin.org.au/austinjspui/handle/1/11407
DOI: 10.1113/expphysiol.2011.063156
URL: http://www.ncbi.nlm.nih.gov/pubmed/22198016
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.pharmacology.therapeutic use
Animals
Gene Expression Regulation, Enzymologic
Hypertension.drug therapy.enzymology
Hypertrophy, Left Ventricular.drug therapy.enzymology
Kidney Failure, Chronic.drug therapy.enzymology
Myocardium.metabolism.pathology
Nephrectomy
Peptidyl-Dipeptidase A.biosynthesis.deficiency.genetics
Ramipril.pharmacology.therapeutic use
Rats
Rats, Sprague-Dawley
Treatment Outcome
Appears in Collections:Journal articles

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