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: Duncan J Campbell, Christopher J Zeitz, Murray D Esler, John D Horowitz
• Journal: Journal of hypertension (J Hypertens) Vol. 22 Issue 10 Pg. 1971-6 (Oct 2004) ISSN: 0263-6352 [Print] England
• PMID: 15361769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Angiotensins
• Peptide Fragments
• Angiotensin II
• Angiotensin I
• Carboxypeptidases
• Peptidyl-Dipeptidase A
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2
• angiotensin I (1-7)

Topics

• Adult
• Angiotensin I (blood)
• Angiotensin II (blood)
• Angiotensin-Converting Enzyme 2
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage, therapeutic use)
• Angiotensins (blood)
• Carboxypeptidases (physiology)
• Cardiac Output, Low (blood, drug therapy)
• Case-Control Studies
• Coronary Circulation
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Peptide Fragments (blood)
• Peptidyl-Dipeptidase A