Document Detail

Early captopril treatment inhibits DNA synthesis in endothelial cells and normalization of maximal coronary flow in infarcted rat hearts.
MedLine Citation:
PMID:  9876328     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Cardiac remodeling due to myocardial infarction (MI) includes myocyte hypertrophy, collagen deposition, a rise in DNA synthesis, and normalization of initially diminished maximal coronary bloodflow. Previously, we demonstrated that early captopril treatment can prevent the rise in total DNA synthesis, collagen deposition and hypertrophy. In the present experiments, we investigated the effects of captopril or perindoprilat treatment on cardiac endothelial cell proliferation and maximal coronary flow.
METHODS: MI was induced by ligation of the left coronary artery in Wistar rats. Sham-operated and infarcted rats were treated with captopril (12 mg/kg.d s.c.) from either day 0-21 (early) or day 21-35 (late) after surgery. In isolated retrogradely perfused rat hearts, maximal coronary flow was determined following maximal dilatation with nitroprusside and adenosine (1 mM each). In separate groups, sections of hearts of sham-operated and MI rats treated with BrdU (day 7-14) and either captopril or perindoprilat (1 mg/kg.d s.c.; day 0-14) were double stained with a monoclonal anti-BrdU antibody and the lectin GSI. The total fraction of DNA synthesizing cells and its proportion of endothelial cells was determined.
RESULTS: Maximal coronary flow was completely normalized in MI hearts within three weeks after surgery. Early captopril, but not late captopril, inhibited the normalization of maximal coronary flow in MI hearts (Early: sham, 27.4 +/- 1.0; MI, 21.2 +/- 1.4 ml/min; P < 0.05; mean +/- SEM) without affecting the hypertrophic response. The total fraction of DNA synthesizing cells was significantly increased in MI hearts (sham: 7.6 +/- 1.9; MI: 14.9 +/- 2.2%). The proportion of endothelial cells, however, was comparable in sham-operated and infarcted hearts (sham: 30 +/- 3; MI: 33 +/- 3%). Both early captopril and perindoprilat treatment inhibited total DNA synthesis in MI hearts. Only in captopril pre-treated hearts, this inhibition was associated with a disproportionate inhibition of the endothelial cell proliferation (10.3 +/- 2.0%).
CONCLUSION: Early captopril treatment inhibits endothelial cell proliferation and coronary vessel growth following MI, which seems to be partly due to inhibition of the renin angiotensin system.
H J Nelissen-Vrancken; M C Kuizinga; M J Daemen; J F Smits
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  40     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1999-02-02     Completed Date:  1999-02-02     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  156-64     Citation Subset:  IM    
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
Captopril / therapeutic use*
Coronary Circulation / drug effects*
DNA / biosynthesis*
Drug Implants
Endothelium, Vascular / drug effects,  metabolism*,  pathology
Indoles / therapeutic use
Myocardial Infarction / drug therapy*,  metabolism,  pathology
Rats, Wistar
Time Factors
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Drug Implants; 0/Indoles; 2UV6ZNQ92K/perindoprilat; 9007-49-2/DNA; 9G64RSX1XD/Captopril

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