Document Detail


Evidence against a major role for angiotensin converting enzyme-related carboxypeptidase (ACE2) in angiotensin peptide metabolism in the human coronary circulation.
MedLine Citation:
PMID:  15361769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  22     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-13     Completed Date:  2005-01-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1971-6     Citation Subset:  IM    
Affiliation:
St Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia. dcampbell@svi.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adult
Angiotensin I / blood
Angiotensin II / blood
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
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Angiotensins; 0/Peptide Fragments; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 9041-90-1/Angiotensin I; EC 3.4.-/Carboxypeptidases; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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