Changes in luminal flow rate modulate basal and bradykinin‐stimulated cell [Ca2+] in aortic endothelium

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Abstract
Hemodynamic forces influence many endothelial cell functions. The coupling between hemodynamic forces and cell function could be mediated by mechano-sensitive ion channels present in the plasma membrane of endothelial cells. Because one of these channels is permeable to Ca2+, we tested whether hemodynamic forces influence endothelial cell Ca2+ ([Ca2+]i). Bovine aortic endothelial cells were grown inside cylindrical glass tubes, loaded with fura-2, and perfused at different pressures and flow rates on the stage of a fluorescence microscope. Decreasing flow from 110 to 2 ml.min−1 raised [Ca2+]i from 57 ± 11 to 186 ± 29 nM (mean ± SEM, p < 0.01) by increasing the entry of extracellular Ca2+ into the cytoplasm. Increasing flow from 2 to 110 ml.min−1 transiently decreased [Ca2+]i from 62 ± 3 to 33 ± 5 nM (p < 0.01) apparently due to reduced Ca2+ entry and concomitant extrusion by the plasma membrane Ca2+-ATPase. The rise in [Ca2+]i induced by bradykinin was magnified during a decrease in flow; in control cells, 10−7 M bradykinin increased [Ca2+]i by 162 ± 26 nM, whereas [Ca2+]i increased 350 ± 67 nM (p < 0.05) in cells previously exposed to 110 ml.min−1. These observations suggest that flow-induced changes in [Ca2+]i might be a signal-transduction mechanism for endothelial functions responsive to hemodynamic forces and may also modulate the magnitude of hormonally mediated increases in [Ca2+]i.