Changes in luminal flow rate modulate basal and bradykinin-stimulated cell [Ca2+] in aortic endothelium.
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 less than 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 less than 0.01) apparently due to reduced Ca2+ entry and concomitant extrusion by the plasma membrane Ca(2+)-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 less than 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.
Oliver
J A
JA
Department of Medicine, Columbia University, New York, New York 10032.
Chase
H S
HS
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016257:Fura-2; D006439:Hemodynamics / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D000252:Calcium-Transporting ATPases; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2