Captopril and enalaprilat decrease antioxidant defences in human endothelial cells and are unable to protect against apoptosis

Authors

  • Agnès Mailloux,

    1. Service de Biochimie A, Hôpital Saint-Antoine AP-HP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
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  • Benjamin Deslandes,

    1. Service de Biochimie A, Hôpital Saint-Antoine AP-HP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
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  • Michel Vaubourdolle,

    1. Service de Biochimie A, Hôpital Saint-Antoine AP-HP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
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  • Bruno Baudin

    Corresponding author
    1. Service de Biochimie A, Hôpital Saint-Antoine AP-HP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France
    2. GRECAN (EA-1772) UFR des Sciences Pharmaceutiques, Université de Caen-Basse Normandie, boulevard Becquerel, 14032 Caen Cedex, France
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Corresponding author bruno.baudin@sat.ap-hop-paris.fr

Abstract

Angiotensin-converting enzyme (ACE) inhibitors were shown to improve endothelial dysfunction in various human diseases and some of these inhibitors have been proposed as enhancers of antioxidant defences. We measured glutathione peroxidase (GPX), superoxide dismutase (SOD) and malondialdehyde (MDA) in human endothelial cells treated with captopril or enalaprilat, two ACE inhibitors, and we showed that both inhibitors decreased GPX and SOD activities but not MDA, the end-product of lipoperoxidation. Captopril and enalaprilat were also unable to protect against etoposide-induced apoptosis in endothelial cells, indicating that they cannot be considered as protective drugs for the endothelium, in particular in clinical situations involving oxidative stress or apoptosis. Moreover, when used at high concentration captopril, but not enalaprilat, was toxic for endothelial cells with both necrotic and apoptotic effects.

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