Shear stress increases inositol trisphosphate levels in human endothelial cells

To elucidate some of the early mechanisms underlying the response of primary human endothelial cells to the initiation of flow, we investigated the changes in inositol lipid metabolism in cells exposed to arterial and venous levels of shear stress. We used a radioimmunoassay specific for inositol-1,4,5-trisphosphate (Ins1,4,5P3) to demonstrate that initiation of an arterial shear stress caused a rapid rise in Ins1,4,5P3 levels which peaked after approximately 30 seconds of flow (2.1 +/- 0.2 fold stimulation) and remained elevated for at least 6 minutes after the initiation of flow. This increased Ins1,4,5P3 concentration is similar in magnitude to the increase caused by 10 microM histamine (2.8 +/- 0.3 fold stimulation). Thus these cells may detect the presence of mechanical stress by a signal transduction pathway involving inositol lipid metabolism.