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Am J Physiol Renal Physiol (November 12, 2008). doi:10.1152/ajprenal.90488.2008
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Submitted on August 13, 2008
Revised on September 30, 2008
Accepted on November 10, 2008

Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan

María José Soler1, Minghao Ye1, Jan Wysocki1, Josette William1, Josep Lloveras2, and Daniel Batlle1*

1 Northwestern University Medical School
2 Hospital del Mar-IMIM

* To whom correspondence should be addressed. E-mail: d-batlle{at}northwestern.edu.

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 were performed in renal arterioles isolated by laser capture microdissection using real time PCR. In renal arterioles, ACE was localized in the endothelial layer, whereas ACE2 was localized in the tunica media. In mice treated with telmisartan (2mg/kg/day) for 2 weeks, ACE2 expression was increased by immunostaining whereas ACE expression was decreased. This was reflected in a decrease in the ACE/ACE2 ratio as compared to vehicle (0.53±0.14 vs 7.59±2.72, p=0.027, respectively). In renal arterioles isolated by laser microdissection, the ACE/ACE2 mRNA ratio was also decreased as compared to control mice (1.21±0.31 vs 4.63±0.86, p=0.044, respectively). In conclusion, in renal 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.




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Am. J. Physiol. Renal Physiol.Home page
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Am J Physiol Renal Physiol, September 1, 2009; 297(3): F802 - F808.
[Abstract] [Full Text] [PDF]




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