Published in:
01-08-2004 | Experimental
Effects of the angiotensin-converting enzyme inhibitor perindopril on endothelial injury and hemostasis in rabbit endotoxic shock
Published in: Intensive Care Medicine | Issue 8/2004
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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 mg.kg−1, 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 (Emax=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.