title: Evidence against a major role for angiotensin converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation.
abstract: OBJECTIVE
  To investigate the role of angiotensin-converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation.
  
  
  METHODS
  Angiotensin I and angiotensin II, and their respective carboxypeptidase metabolites, angiotensin-(1-9) and angiotensin-(1-7), were measured in arterial and coronary sinus blood of heart failure subjects receiving angiotensin-converting enzyme (ACE) inhibitor therapy and in normal subjects not receiving ACE inhibitor therapy. In addition, angiotensin I, angiotensin II and angiotensin-(1-7) were measured in arterial and coronary sinus blood of subjects with coronary artery disease before, and at 2, 5 and 10 min after, intravenous administration of ACE inhibitor.
  
  
  RESULTS
  In comparison with normal subjects, heart failure subjects receiving ACE inhibitor therapy had a greater than 40-fold increase in angiotensin I levels, but angiotensin-(1-9) levels were low (1-2 fmol/ml), and similar to those of normal subjects. Moreover, angiotensin-(1-7) levels increased in parallel with angiotensin I levels and the angiotensin-(1-7)/angiotensin II ratio increased by 7.5-fold in coronary sinus blood. Intravenous administration of ACE inhibitor to subjects with coronary artery disease rapidly decreased angiotensin II levels by 54-58% and increased angiotensin I levels by 2.4- to 2.8-fold, but did not alter angiotensin-(1-7) levels or net angiotensin-(1-7) production across the myocardial vascular bed.
  
  
  CONCLUSIONS
  The failure of angiotensin-(1-9) levels to increase in response to increased angiotensin I levels indicated little role for ACE2 in angiotensin I metabolism. Additionally, the levels of angiotensin-(1-7) were more linked to those of angiotensin I than angiotensin II, consistent with its formation by endopeptidase-mediated metabolism of angiotensin I, rather than by ACE2-mediated metabolism of angiotensin II.
authors.affiliation: St Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia. dcampbell@svi.edu.au
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Zeitz
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.forename: John D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D000328:Adult; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000809:Angiotensins / Q000097:blood*; D002268:Carboxypeptidases / Q000502:physiology*; D002303:Cardiac Output, Low / Q000097:blood* / Q000188:drug therapy; D016022:Case-Control Studies; D003326:Coronary Circulation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D007703:Peptidyl-Dipeptidase A
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)