Document Detail

Effects of the angiotensin-converting enzyme inhibitor perindopril on endothelial injury and hemostasis in rabbit endotoxic shock.
MedLine Citation:
PMID:  15024568     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To assess the effects of the angiotensin-converting enzyme (ACE) inhibitor (ACEI) perindopril on prolonged endothelial cell dysfunction in a rabbit endotoxic model. DESIGN: Randomized, controlled, interventional trial. SETTING: University animal laboratory. SUBJECTS: A total of 65 male New Zealand White rabbits, randomly assigned to one of eight groups. INTERVENTIONS: Endotoxic shock was induced by a single lipopolysaccharide (LPS, serotype O55:B5) bolus (0.5, i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor (TF) were determined by functional assay. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess endothelial injury of the abdominal aorta. These parameters were studied 5 days (D5) after the onset of endotoxic shock. Rabbits were randomized to receive perindopril (1 mg kg(-1) day(-1) orally) alone, or with N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg kg(-1) day(-1) orally), or L-NAME alone initiated 7 days before the onset of endotoxic shock and maintained for 5 days afterward. MEASUREMENTS AND RESULTS: Perindopril prevented altered endothelium-dependent relaxation to acetylcholine induced by LPS injection (E(max)=75.6+/-3.7 vs 42.3+/-9.4% in LPS group, p<0.05). This effect was inhibited by co-treatment with L-NAME. Perindopril had no effect on either LPS-induced endothelial histological injury or monocyte TF expression. CONCLUSION: These data suggest that perindopril can prevent endothelial dysfunction in endotoxin-induced shock through an NO-dependent mechanism.
Eric Wiel; Qian Pu; Jérôme Leclerc; Delphine Corseaux; Régis Bordet; Niels Lund; Brigitte Jude; Benoît Vallet
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Publication Detail:
Type:  Journal Article     Date:  2004-03-13
Journal Detail:
Title:  Intensive care medicine     Volume:  30     ISSN:  0342-4642     ISO Abbreviation:  Intensive Care Med     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-04     Completed Date:  2004-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7704851     Medline TA:  Intensive Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1652-9     Citation Subset:  IM    
Department of Anesthesiology, Lille University Hospital, Lille, France.
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MeSH Terms
Analysis of Variance
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Blood Gas Analysis
Disease Models, Animal
Endothelium, Vascular / drug effects*,  physiopathology
Hemostasis / drug effects*
NG-Nitroarginine Methyl Ester / pharmacology
Perindopril / pharmacology*
Regression Analysis
Shock, Septic / chemically induced,  physiopathology*
Statistics, Nonparametric
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 50903-99-6/NG-Nitroarginine Methyl Ester; 82834-16-0/Perindopril

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

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