Evidence Against a Major Role for Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2) in Angiotensin Peptide Metabolism in the Human Coronary Circulation

J Hypertens. 2004 Oct;22(10):1971-6. doi: 10.1097/00004872-200410000-00020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin I / blood
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Angiotensins / blood*
  • Carboxypeptidases / physiology*
  • Cardiac Output, Low / blood*
  • Cardiac Output, Low / drug therapy
  • Case-Control Studies
  • Coronary Circulation*
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Peptidyl-Dipeptidase A

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensins
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2
  • angiotensin I (1-7)