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Predominance of ACE2‐Dependent Metabolism of Angiotensin II But Not Angiotensin I In Sheep Renal Proximal Tubules and Urine
Author(s) -
Shaltout Hossam A,
Westwood Brian,
Averill David,
Figueroa Jorge,
Ferrario Carlos,
Diz Debra,
Rose James,
Chappell Mark
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a765-d
Subject(s) - renin–angiotensin system , endocrinology , medicine , angiotensin converting enzyme 2 , angiotensin ii , kidney , neprilysin , chemistry , enzyme , losartan , angiotensin converting enzyme , metabolism , urine , biology , biochemistry , blood pressure , disease , covid-19 , infectious disease (medical specialty)
The renin‐angiotensin system (RAS) is an essential regulator of cardiovascular function. Although renin and angiotensin converting enzyme (ACE) are the key enzymes of this system, the novel enzyme ACE2 suggests alternative processing within the RAS. In the present study, we assessed the distribution and activity of ACE2 in the sheep kidney. Immunocytochemical analysis of ACE2 revealed predominant staining in the proximal tubules of the inner cortex of the kidney and the lack of staining in glomerular areas. ACE2 activity was then determined in isolated proximal tubules by a sensitive HPLC method using 125I‐Ang I or Ang II as substrates. Addition of Ang II to the tubules resulted in the production of Ang‐(1–7) and Ang‐(1–4). ACE2 inhibition blocked the majority [>80%, n=3] of both Ang‐(1–7) and Ang‐(1–4) formation. Neprilysin inhibition reduced the formation of Ang‐(1–4) but not Ang‐(1–7). Ang I was converted to Ang II [46%] and Ang‐(1–7) [13%]. ACE inhibition blocked Ang II formation [>90%] and reduced Ang‐(1–7). ACE2 inhibition also attenuated the formation of Ang‐(1–7) [>80%] but increased Ang II. In the urine, Ang‐(1–7) was also the principal product from ACE2. We did not detect ACE2‐dependant metabolism of Ang I in the proximal tubule or urine (n=3). In summary, Ang‐(1–7) was the primary product from the ACE2‐dependent metabolism of Ang II in the tubules and urine. We conclude that ACE2 is a component of the RAS cascade to balance the expression of Ang II and Ang‐(1–7) within the kidney. Support: HD047584, HL56973, HL51952.