Stimulation of adenylate cyclase activity in cultured endothelial cells subjected to cyclic stretch.

While vascular endothelial cells are repeatedly stretched by the pulsatile nature of cardiac output, in vitro models traditionally used to study vascular biology involve static culture techniques. We have recently shown that pulsatile stretching of endothelial cells in culture will increase their rates of proliferation and regulate their secretion of macromolecules. The aim of this study was to determine whether membrane adenylate cyclase is involved in intracellular signalling during pulsatile stress. Bovine aortic endothelial cells were seeded on flexible-bottomed culture wells (3 x 10(5) cells/25 mm well) and allowed to attach for 48 hours. The culture wells were placed in a vacuum-operated stress providing instrument and subjected to 0.5 s of 24% strain, 0.5 s relaxation (60 cycles/min) for 0, 1, 3, 5, 7, 10 and 15 minutes (N = 24 wells/time point). Cells were homogenized and a crude membrane preparation (27,000 x g) was assayed for adenylate cyclase under basal and forskolin (100 microM) stimulated conditions. The results indicate that there is a time-dependent increase in both basal and stimulated adenylate cyclase with cyclic deformation and suggest that there may be a "stretch receptor" coupled to adenylate cyclase which can modulate endothelial cell function with hemodynamic changes.