Key Points
- To investigate the direct effect of pure hydrostatic pressure, independent of shear stress or mechanical stretch, on endothelin-1 release in endothelial cells.
- Exposed cultured human umbilical vein endothelial cells (HUVECs) to pure pressure elevation without shear stress or stretch.
- Treated cells with pharmacological inhibitors targeting calcium channels (nifedipine), stretch-activated channels (gadolinium), phospholipase C, protein kinase C (H-7, chelerythrine), and nitric oxide synthase (L-NMMA) to identify underlying signaling mechanisms.
- Elevated pressure significantly stimulated endothelin-1 secretion and decreased basal nitric oxide release from cultured endothelial cells.
- Inhibition of phospholipase C and protein kinase C significantly attenuated the pressure-induced increase in endothelin-1 release.
- Blockade of calcium channels with nifedipine, stretch-activated channels with gadolinium, or nitric oxide synthase with L-NMMA had no inhibitory effect on pressure-induced endothelin-1 release.
Structured PICO
PPopulationCultured human umbilical vein endothelial cells
IInterventionElevation of pure pressure without shear stress or stretch
CComparatorBasal conditions (no pressure elevation)
OOutcomeEndothelin-1 releasesurrogate
Pure pressure enhances endothelin-1 release from human endothelial cells partially through activation of phospholipase C and protein kinase C.