Document Detail


Effect of reduced angiotensin-converting enzyme gene expression and angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptide levels in mice.
MedLine Citation:
PMID:  14769811     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is uncertainty about the contribution of angiotensin-converting enzyme (ACE) to angiotensin II formation, with recent studies suggesting that non-ACE enzymes may be the predominant pathway of angiotensin II formation in kidney, heart, and lung. To investigate the role of ACE in angiotensin II formation, we measured angiotensin I and II levels in blood, kidney, and heart of 2 mouse genetic models (ACE.1 and ACE.4) of reduced somatic ACE gene expression and in blood, kidney, heart, lung, adrenal, and brain of mice administered the ACE inhibitor lisinopril. We also measured the levels of bradykinin (1-9) and its ACE metabolite bradykinin (1-7). Reduced ACE gene expression and ACE inhibition had similar effects on angiotensin and bradykinin peptide levels. Angiotensin II levels were reduced by 70% to 97% in blood, 92% to 99% in kidney, 93% to 99% in heart, 97% in lung, and 85% in adrenal and brain. The marked reductions in angiotensin II/angiotensin I ratio indicated that ACE was responsible for at least 90% of angiotensin I conversion to angiotensin II in blood, kidney, heart, lung, and brain, and at least 77% in adrenal. Blood bradykinin (1-9) levels were increased 6.4-fold to 8.4-fold. Heart bradykinin (1-9) levels were increased in ACE.4 mice and the bradykinin (1-7)/bradykinin (1-9) ratio was reduced in kidney and heart of ACE.4 mice and heart of lisinopril-treated mice. These studies demonstrate that ACE is the predominant pathway of angiotensin II formation in blood and tissues of mice and plays a major role in bradykinin (1-9) metabolism in blood and, to a lesser extent, in kidney and heart.
Authors:
Duncan J Campbell; Theodora Alexiou; Hong D Xiao; Sebastien Fuchs; Michael J McKinley; Pierre Corvol; Kenneth E Bernstein
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-02-09
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-26     Completed Date:  2004-08-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  854-9     Citation Subset:  IM    
Affiliation:
St. Vincent's Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia. J.Campbell@medicine.unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
Adrenal Glands / enzymology
Angiotensin I / metabolism*
Angiotensin II / metabolism*
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Animals
Bradykinin / metabolism*
Brain / enzymology
Enzyme Induction
Female
Kidney / enzymology*
Lisinopril / pharmacology
Lung / enzymology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / enzymology*
Organ Specificity
Peptide Fragments / metabolism*
Peptidyl-Dipeptidase A / deficiency*,  genetics,  physiology
Grant Support
ID/Acronym/Agency:
DK39777/DK/NIDDK NIH HHS; DK44280/DK/NIDDK NIH HHS; DK51445/DK/NIDDK NIH HHS; DK55503/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Peptide Fragments; 11128-99-7/Angiotensin II; 58-82-2/Bradykinin; 83915-83-7/Lisinopril; 9041-90-1/Angiotensin I; EC 3.4.15.1/Peptidyl-Dipeptidase A

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


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