1. ¹Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
2. ²Department of Nephrology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain
3. ³Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Correspondence: D Batlle, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. E-mail: d-batlle@northwestern.edu

Received 21 November 2006; Revised 12 April 2007; Accepted 1 May 2007; Published online 20 June 2007.

Abstract

Angiotensin converting enzyme 2 (ACE2) is localized to the glomerular epithelial cells. Since ACE2 promotes the degradation of angiotensin II, a decrease in ACE2 activity could lead to the development of glomerular injury. We gave a specific ACE2 inhibitor, MLN-4760, for 4 weeks to mice rendered diabetic with streptozotocin. The urinary albumin/creatinine ratio was increased along with expansion of the glomerular matrix in diabetic mice treated with the inhibitor compared to the vehicle-treated mice. Glomerular staining of ACE was increased in the diabetic group and was further significantly increased in the diabetic group treated with MLN-4760. In renal vessels, ACE expression was also increased in the diabetic mice and, again, further increased in those diabetic mice treated with the ACE2 inhibitor. Our study shows that chronic pharmacologic ACE2 inhibition worsens glomerular injury in streptozotocin-induced diabetic mice in association with increased ACE expression.