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Enalapril does not alter adhesion molecule levels in human endotoxemia
Monika Graninger1, Claudia Marsik, Tanja Dukic
1Department of Clinical Pharmacology and Division of Angiology, Vienna University, Vienna, Austria.
Shock (Augusta, Ga.)
|May 15, 2003
Summary
Enalapril, an ACE inhibitor, did not affect markers of endothelial activation in healthy volunteers after endotoxin challenge. This suggests enalapril may not offer clinical benefits in sepsis.
Area of Science:
- Pharmacology
- Immunology
- Critical Care Medicine
Background:
- Angiotensin-converting enzyme inhibitors (ACE-I) like enalapril may lower circulating adhesion molecules (cAM) in critically ill patients.
- The precise mechanisms behind this potential benefit require further investigation.
Purpose of the Study:
- To investigate the acute effects of enalapril on endotoxin-induced, cytokine-mediated upregulation of cAM in healthy individuals.
- To determine if ACE inhibition influences plasma indices of endothelial activation following endotoxin infusion.
Main Methods:
- A randomized, controlled trial involving 30 healthy male volunteers.
- Participants received placebo, enalapril for 5 days, or a single dose of enalapril before lipopolysaccharide (LPS) infusion.
- Measurements included TNF levels, cAM (E-selectin, P-selectin, VCAM-1, ICAM-1, von Willebrand factor), and monocyte expression of ICAM-1 and CD11b.
Main Results:
- LPS infusion significantly increased TNF, cAM, and monocyte expression markers.
- No significant differences in these markers were observed between enalapril and placebo treatment groups.
- Enalapril achieved 95% inhibition of ACE activity without altering the measured indices of endothelial activation.
Conclusions:
- Inhibition of ACE activity by enalapril does not influence plasma indices of endothelial activation after endotoxin infusion in healthy individuals.
- The findings do not support a beneficial clinical effect of enalaprilat in septicemia.