Wall shear stress rather than shear rate regulates cytoplasmic Ca++ responses to flow in vascular endothelial cells.
Recent evidence suggests that the vascular endothelial cell (EC) can sense the flow-rate over its surface and according to the information, regulates not only its own morphology and functions but also those of the surrounding smooth muscle and other tissues. There is now a discussion over which of the following mechanisms actually initiates the signal-transacting response of EC against flow: the mechanical shear deformation of the cell due to flow-oriented wall shear stress (tau), or the diffusional accumulation of vasoactive agonists on the cell surface modulated by wall shear rate (gamma) or both. To identify the relative importance of each mechanism, we examined quantitative changes in the cytoplasmic free Ca++ concentration ([Ca++]i) in cultured EC in the presence of the Ca++ mobilizing agonist ATP, i.e., a second messenger response of the internal signalling system, following the perfusion of two buffers with different viscosities (mu), which relates these factors as tau = mu gamma. The results of in vitro fluorescence photometry in EC with Fura-2 showed that the [Ca++]i level was enhanced with increase in the shear rate but to a greater extent with higher viscosity, and that the [Ca++]i levels at the same calculated level of shear stress were virtually identical, regardless of difference in shear rate and viscosity. This quantitative one-to-one relationship between the shear stress and the second messenger response suggests that wall shear stress rather than wall shear rate is the principal physical factor eliciting EC responses to flow.
Ando
J
J
Department of Cardiovascular Biomechanics, Faculty of Medicine, University of Tokyo, Japan.
Ohtsuka
A
A
Korenaga
R
R
Kawamura
T
T
Kamiya
A
A
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D003593:Cytoplasm / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D012212:Rheology; D014783:Viscosity
D003470:Culture Media; D002118:Calcium