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Am J Physiol Renal Physiol 296: F398-F405, 2009. First published November 12, 2008; doi:10.1152/ajprenal.90488.2008
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Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan

María José Soler,1 Minghao Ye,1 Jan Wysocki,1 Josette William,1 Josep Lloveras,2 and Daniel Batlle1

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

Submitted 13 August 2008 ; accepted in final form 10 November 2008

Angiotensin-converting enzyme (ACE)2 is a carboxypeptidase that degrades angiotensin II and other peptides. In the kidney, ACE2 localization within the glomerulus and tubules is cell specific. This study was aimed to investigate the localization of ACE2 within the renal vasculature. We also studied the effect of the administration of a specific angiotensin II type 1 receptor blocker, telmisartan, on ACE2 expression in the renal vasculature. ACE2 and ACE were localized in renal arterioles using confocal microscopy and specific cell markers. Quantitative measurements of ACE2 and ACE mRNA were estimated in kidney arterioles isolated by laser capture microdissection using real-time PCR. In kidney arterioles, ACE was localized in the endothelial layer, whereas ACE2 was localized in the tunica media. In mice treated with telmisartan (2 mg·kg–1·day–1) for 2 wk, ACE2 expression was increased by immunostaining, whereas ACE expression was decreased. This was reflected in a decrease in the ACE/ACE2 ratio compared with vehicle-treated controls (0.53 ± 0.14 vs. 7.59 ± 2.72, P = 0.027, respectively). In kidney arterioles isolated by laser capture microdissection, the ACE/ACE2 mRNA ratio was also decreased compared with control mice (1.21 ± 0.31 vs. 4.63 ± 0.86, P = 0.044, respectively). In conclusion, in kidney arterioles ACE2 is preferentially localized in the tunica media, and its expression is increased after administration of the angiotensin II type 1 receptor blocker, telmisartan. Amplification of ACE2 in the renal vasculature may contribute to the therapeutic action of telmisartan by increasing angiotensin II degradation.

kidney vessels; angiotensin-converting enzyme; laser microcapture



Address for reprint requests and other correspondence: D. Batlle, Division of Nephrology and Hypertension, Dept. of Medicine, The Feinberg School of Medicine, Northwestern Univ., 320 E Superior, Chicago, IL 60611 (e-mail: d-batlle{at}northwestern.edu)




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