Auswirkungen einer Blockade des Angiotensin Converting Enzyms durch Enalapril auf die Aktivierung von Endothelzellen und Leukozyten bei systemischer Entzündung induziert durch Lipopolysaccharide

In dieser Studie untersuchte man die Auswirkungen eines ACE-Inhibitors Enalapril in einer LPS induzierten, TNF-Alpha vermittelten systemischen Entzündung und betrachtete, ob eine Verminderung der erhöhten Adhäsionsmoleküle während einer Sepsis durch Enalapril gesenkt werden könnte. 30 männliche Pro...

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Bibliographic Details
Main Author: Dukic, Tanja
Contributors: Czubayko, F. (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2006
Pharmakologisches Institut
Subjects:
LPS
Online Access:PDF Full Text
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Table of Contents: The angiotensin-converting enzyme inhibitor (ACE-I) enalapril has been shown to lower elevated levels of circulating adhesion molecules (cAM) in critically ill patients. To delineate the mechanisms of this possibly beneficial effect of enalapril, we studied the acute effects of enalapril in a well-defined model of endotoxin-triggered, cytokine-mediated cAM up-regulation. In a randomized, controlled trial, 30 healthy male volunteers received 2 ng/kg lipopolysaccharide (LPS)after pretreatment with placebo or 20 mg/day enalapril for 5 days or with a single dose of 20 mg of enalapril 2 h before LPS infusion. LPS infusion increased TNF levels 300-fold above normal, circulating (c) E-selectin levels by 425% (CI,359%–492%), VCAM-1 and ICAM-1. LPS infusion also enhanced ICAM-1 and CD11b expression 2- to 3-fold on monocytes. However, no differences were seen between treatment groups (P > 0.05), despite 95% inhibition of ACE activity by enalapril. Inhibition of ACE activity by enalapril does not influence plasma indices of endothelial activation after endotoxin infusion in healthy individuals. Our results do not support the concept of a beneficial clinical effect of enalaprilat in septicemia.