Influence of Reduced Intracellular Glutathione Availability on the Secretion of Vasoactive Substances by Human Umbilical Vein Endothelial Cells

Abstract

Objective. Oxidative stress might be the reason for endothelial dysfunction in preeclampsia. The glutathione—peroxidase system is one of the primary antioxidants in the endothelium. We tested the effect of oxidative stress by reduction of glutathione availability on the secretion of vasoactive substances in endothelial cells.

Methods. Endothelial cells in culture were incubated with different concentrations of buthionine-[S,R]-sulfoximine (BSO) or 1-chloro-2,4-dinitrobenzene (CDNB), both leading to a reduced intracellular availability of glutathione. The secretion of the vasoactive substances nitric oxide (NO), endothelin-I (ET-1), and prostacyclin (PGI₂) was measured with respect to vitality and proliferation rate of the endothelial cells in culture.

Main Outcome Measure. Effect of oxidative stress on the secretion of vasoactive substances from endothelial cells.

Results. The oxidants CDNB and BSO have (in concentrations before evidence of cytotoxicity) a stimulating effect on the production of PGI₂, they inhibit NO availability, and they do not significantly interfere with ET-1 production.

Conclusion. Oxidative stress in vitro induces an imbalance in the secretion of NO, ET-1, and PGI₂ in endothelial cells.

Key Words:

• Preeclampsia
• Endothelial cells
• Oxidative stress
• Glutathione