Document Detail


Cardiac angiotensin converting enzyme overproduction indicates interstitial activation in renovascular hypertension.
MedLine Citation:
PMID:  7585810     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after clipping, and determined the cellular distribution of its increase in the left ventricle of 2K-1C hypertensive rats. METHODS: Cardiac ACE activity was quantified in left and right ventricles using a radiolabeled synthetic ACE substrate, and ACE mRNA steady-state level was quantified by ribonuclease protection assay. Tissue localization of ACE in normal and hypertrophied hearts was determined by measuring ACE activity in isolated ventricular cells. In situ hybridization with a rat ACE cDNA and immunohistochemistry with a monoclonal anti-ACE antibody were used to identify tissue compartments producing ACE mRNA and protein. RESULTS: The left ventricle was hypertrophied 2 weeks after clipping and remained hypertrophied at 12 weeks. Left ventricular ACE activity was significantly increased 2 and 4 weeks (3.2 +/- 0.3 in 2K-1C vs. 1.7 +/- 0.1 pmol/mg prot/min in sham-operated rat) after renal artery clipping, but not at 12 weeks. The right ventricle was slightly hypertrophied 4 weeks after clipping and remained hypertrophied at 12 weeks. Right ventricular ACE activity was significantly increased at 4 (6.7 +/- 0.6 in 2K-1C vs. 3.1 +/- 0.3 pmol/mg prot/min in sham-operated rat) and 12 weeks. ACE activity was not detectable in cardiomyocytes isolated by Percoll gradient. Neither was ACE mRNA detected in isolated cardiomyocytes, even after ACE mRNA amplification by RT-PCR. In contrast, ACE activity and mRNA were detected in pooled non-cardiomyocytic cells. Thus the increase in cardiac ACE activity associated with hypertension must be due to an increase in ACE expression by non-cardiomyocytic cells. In situ hybridization showed an autoradiographic signal for ACE mRNA over the endothelial cells of coronary arteries and over the interstitial spaces including pericoronary and fibrosis areas. Immunohistochemistry confirmed these data, showing ACE on endothelial cells and in pericoronary spaces with an increased signal in pericoronary and fibrosed areas in hypertensive hypertrophied left ventricle. CONCLUSION: Besides its usual endothelial expression, ACE is absent from cardiomyocytes and present in interstitial tissue, in the pericoronary spaces in normal tissue and more markedly in hypertrophied ventricles.
Authors:
M Challah; A Nicoletti; J F Arnal; M Philippe; I Laboulandine; J Allegrini; F Alhenc-Gelas; S Danilov; J B Michel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  30     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-12     Completed Date:  1995-12-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  231-9     Citation Subset:  IM    
Affiliation:
U-367 INSERM, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / blood
Animals
Cell Membrane / enzymology
Enzyme Activation
Extracellular Space / enzymology
Hypertension, Renovascular / blood,  enzymology*
Immunohistochemistry
In Situ Hybridization
Male
Myocardium / enzymology*
Peptidyl-Dipeptidase A / genetics,  metabolism*
Polymerase Chain Reaction
RNA, Messenger / analysis
Rats
Rats, Wistar
Renin / blood
Chemical
Reg. No./Substance:
0/RNA, Messenger; 11128-99-7/Angiotensin II; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.23.15/Renin

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