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dc.contributor.authorBurrell, LM
dc.contributor.authorBurchill, L
dc.contributor.authorDean, RG
dc.contributor.authorGriggs, K
dc.contributor.authorPatel, SK
dc.contributor.authorVelkoska, E
dc.identifierpii: expphysiol.2011.063156
dc.identifier.citationBurrell, L. M., Burchill, L., Dean, R. G., Griggs, K., Patel, S. K. & Velkoska, E. (2012). Chronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition. EXPERIMENTAL PHYSIOLOGY, 97 (4), pp.477-485.
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractRenin-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.
dc.subjectCardiology (incl. Cardiovascular Diseases); Nephrology and Urology; Cardiovascular System and Diseases; Urogenital System and Disorders
dc.titleChronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition
dc.typeJournal Article
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Austin Health
melbourne.source.titleEXPERIMENTAL PHYSIOLOGY
melbourne.contributor.authorBurrell, Louise
melbourne.contributor.authorBURCHILL, LUKE
melbourne.contributor.authorDEAN, RACHAEL
melbourne.contributor.authorGriggs, Karen
melbourne.contributor.authorPatel, Sheila
melbourne.contributor.authorVelkoska, Elena
melbourne.contributor.authorBurchill, Luke
melbourne.fieldofresearch320101 Cardiology (incl. cardiovascular diseases)
melbourne.fieldofresearch320214 Nephrology and urology
melbourne.seocode200199 Clinical health not elsewhere classified
melbourne.accessrightsAccess this item via the Open Access location

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