Soler María José, Ye Minghao, Wysocki Jan, William Josette, Lloveras Josep, Batlle Daniel
Department of Medicine, Division of Nephrology and Hypertension, The Feinberg School of Medicine, Northwestern Univ., 320 E Superior, Chicago, IL 60611, USA.
Am J Physiol Renal Physiol. 2009 Feb;296(2):F398-405. doi: 10.1152/ajprenal.90488.2008. Epub 2008 Nov 12.
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.
血管紧张素转换酶（ACE）2是一种可降解血管紧张素II和其他肽类的羧肽酶。在肾脏中，ACE2在肾小球和肾小管内的定位具有细胞特异性。本研究旨在调查ACE2在肾血管系统中的定位。我们还研究了给予特异性血管紧张素II 1型受体阻滞剂替米沙坦对肾血管系统中ACE2表达的影响。使用共聚焦显微镜和特异性细胞标志物对肾小动脉中的ACE2和ACE进行定位。通过激光捕获显微切割分离肾小动脉，使用实时PCR对ACE2和ACE mRNA进行定量测定。在肾小动脉中，ACE定位于内皮细胞层，而ACE2定位于中膜。在用替米沙坦（2 mg·kg⁻¹·d⁻¹）治疗2周的小鼠中，免疫染色显示ACE2表达增加，而ACE表达减少。与给予赋形剂的对照组相比，ACE/ACE2比值降低（分别为0.53±0.14和7.59±2.72，P = 0.027）。在通过激光捕获显微切割分离的肾小动脉中，与对照小鼠相比，ACE/ACE2 mRNA比值也降低（分别为1.21±0.31和4.63±0.86，P = 0.044）。总之，在肾小动脉中，ACE2优先定位于中膜，并在给予血管紧张素II 1型受体阻滞剂替米沙坦后其表达增加。肾血管系统中ACE2的增加可能通过增加血管紧张素II的降解而有助于替米沙坦的治疗作用。
