Changes in cyclic strain increase inositol trisphosphate and diacylglycerol in endothelial cells

The purpose of this study was to assess the effect of cyclic strain on phosphatidylinositol turnover in cultured bovine aortic endothelial cells (EC). Confluent EC grown on flexible membrane bottoms were deformed by vacuum to 24% maximum strain and subjected to two cyclic strain regimens. In the first set of experiments, EC were subjected to deformation at a frequency of 60 cycles/min for either 0 (stationary control), 1, 5, 10, 25, 50, or 100 cycles of stretch. In the second set of experiments, EC were preconditioned by deforming the membranes at 60 cycles/min for 24 h. The cycling frequency was then acutely increased to 100 cycles/min for 0, 1, 5, 10, 25, or 100 cycles. Inositol phosphate and diacylglycerol concentrations were determined at the end of each regimen. The results demonstrate that either the initiation of pulsatile stretch or an acute change in cyclic stretch frequency stimulates a sequential and transient generation of inositol trisphosphate, its metabolites inositol biphosphate and monophosphate, and diacylglycerol. Thus EC may respond to the initiation and change in cyclic stretch frequency by a signal transduction pathway involving inositol lipid metabolism.