• Eric Wiel, Qian Pu, Jérôme Leclerc, Delphine Corseaux, Régis Bordet, Niels Lund, Brigitte Jude, and Benoît Vallet.
• Department of Anesthesiology, Lille University Hospital, Lille, France.
• Intensive Care Med. 2004 Aug 1; 30 (8): 1652-9.

ObjectiveTo assess the effects of the angiotensin-converting enzyme (ACE) inhibitor (ACEI) perindopril on prolonged endothelial cell dysfunction in a rabbit endotoxic model.DesignRandomized, controlled, interventional trial.SettingUniversity animal laboratory.SubjectsA total of 65 male New Zealand White rabbits, randomly assigned to one of eight groups.InterventionsEndotoxic 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 ResultsPerindopril 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.ConclusionThese data suggest that perindopril can prevent endothelial dysfunction in endotoxin-induced shock through an NO-dependent mechanism.

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