Omeprazole suppresses endothelial calcium response and eNOS Ser1177 phosphorylation in porcine aortic endothelial...

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Function
• Pharmacology

Background:

• Proton pump inhibitors (PPIs) show anticancer potential but may negatively impact vascular biology.
• The effects of high-dose PPIs on endothelial calcium (Ca2+) signaling and endothelium-derived relaxing factor (EDRF) production remain largely unknown.

Purpose of the Study:

• To investigate the impact of high-dose omeprazole on endothelial Ca2+ responses.
• To determine omeprazole's effect on EDRF production in cultured porcine aortic endothelial cells.

Main Methods:

• Primary cultured porcine aortic endothelial cells were treated with varying concentrations of omeprazole (10-1000 μM).
• Bradykinin (BK) and thapsigargin were used to induce Ca2+ responses.
• Endothelial Ca2+ signaling, eNOS phosphorylation, nitric oxide production, and prostaglandin I2 metabolite levels were assessed.

Main Results:

• Omeprazole dose-dependently suppressed both BK- and thapsigargin-induced endothelial Ca2+ responses.
• Omeprazole slightly reduced Ca2+ mobilization from the endoplasmic reticulum but did not affect the ER Ca2+-ATPase.
• Omeprazole decreased BK-induced eNOS phosphorylation at Ser1177 and tended to reduce nitric oxide and prostaglandin I2 production.

Conclusions:

• High-dose omeprazole suppresses store-operated Ca2+ channels and partially inhibits the G protein-coupled receptor/phospholipase C/inositol 1,4,5-triphosphate pathway.
• Omeprazole attenuates Ca2+-dependent eNOS phosphorylation and impairs EDRF production.
• These findings suggest high-dose omeprazole negatively affects vascular endothelial function through intracellular Ca2+ signaling pathways.