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

Area of Science:

• Biochemistry
• Pharmacology
• Cell Biology

Background:

• Angiotensin-converting enzyme (ACE) inhibitors are known to improve endothelial dysfunction.
• Some ACE inhibitors have been investigated for their potential to enhance antioxidant defenses.
• Endothelial cells are crucial in vascular health and susceptible to oxidative stress and apoptosis.

Purpose of the Study:

• To investigate the effects of ACE inhibitors captopril and enalaprilat on antioxidant enzyme activities in human endothelial cells.
• To determine if these ACE inhibitors protect endothelial cells against etoposide-induced apoptosis.
• To assess the potential toxicity of captopril and enalaprilat on endothelial cells.

Main Methods:

• Human endothelial cells were treated with captopril or enalaprilat.
• Activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured.
• Malondialdehyde (MDA) levels and etoposide-induced apoptosis were assessed. Cell toxicity was evaluated at high concentrations.

Main Results:

• Both captopril and enalaprilat decreased GPX and SOD activities in endothelial cells.
• Neither ACE inhibitor affected MDA levels, the end-product of lipoperoxidation.
• Captopril and enalaprilat did not protect against etoposide-induced apoptosis. High concentrations of captopril, but not enalaprilat, induced endothelial cell toxicity (necrosis and apoptosis).

Conclusions:

• ACE inhibitors captopril and enalaprilat do not enhance endothelial antioxidant defenses and offer no protection against apoptosis.
• These drugs cannot be considered protective agents for the endothelium, especially in conditions of oxidative stress or apoptosis.
• Captopril demonstrates dose-dependent toxicity to endothelial cells, highlighting potential risks at higher therapeutic concentrations.