Prevention of Reactive Oxygen-Induced Endothelial Cell Injury by Blocking Its Process

Abstract

Endothelial cell (EC) injury induced by reactive oxygen species (ROS) was investigated and effects of Ca<sup>2+</sup> channel blockers, agents which elevate intracellular cAMP levels ([cAMP]<sub>i</sub>), and protein kinase inhibitors on H<sub>2</sub>O<sub>2</sub>-induced EC injury were analyzed using human umbilical vein EC cultures. Exposure to H<sub>2</sub>O<sub>2</sub> increased intracellular Ca<sup>2+</sup> levels and decreased [cAMP]<sub>i</sub>. Ca<sup>2+</sup> channel blockers, [cAMP]<sub>i</sub>-elevating agents, and protein kinase inhibitors significantly inhibited H<sub>2</sub>O<sub>2</sub>-induced EC injury. Data suggest that H<sub>2</sub>O<sub>2</sub>-induced EC injury is mediated by extracellular Ca<sup>2+</sup> influx, intracellular cAMP efflux, and intracellular signaling, each of which is blocked by Ca<sup>2+</sup> channel blockers, [cAMP]<sub>i</sub>-elevating agents, or protein kinase inhibitors. It is suggested that ischemia/reperfusion injury induced by ROS may be prevented by Ca<sup>2+</sup> channel blockers, [cAMP]<sub>i</sub>-elevating agents, and protein kinase inhibitors.