Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 582

produce stronger Ca 2 + signals, activate IK (primarily) 172 and SK channels. These
K Ca channels trigger an electrochemical current that hyperpolarizes endothelial cells
and spreads from endothelial cells to smooth myocytes, especially at myoendothe-
lial junctions with possible gap junctions between endothelial and smooth muscle
cells through the basement membrane and fenestrae of internal elastic lamina.
Transmitted hyperpolarization causes maximal vessel dilation.
Another signaling pathway can be involved. In endothelial cells, activated
IP 3 R channels of the sarco(endo)plasmic reticulum generate local, high-intensity,
cytosolic Ca 2 + signals; calcium pulsars represent the release of calcium from
intracellular stores through IP 3 R channels to cause a local stationary signal in
endothelial cells [ 1124 ]. They occur primarily in endothelial projections to the
smooth myocytes. Like the first Ca 2 + signaling process, local increase of cytosolic
Ca 2 + concentration due to calcium pulsars activates nearby Ca 2 + -activated K +
channels (K Ca 2.3 and K Ca 3.1) to hyperpolarize endothelial and, subsequently,
smooth muscle cells.
Calcium pulsar- and sparklet-mediated hyperpolarization may work together
with extracellular calcium in the nearby, restricted, extracellular milieu that can
gate inward rectifier K + channel, thereby causing a K + efflux to augment smooth
myocyte hyperpolarization that improve smooth myocyte relaxation.

9.10.6 Other Mechanotransduction Effects

Endothelial cells that can form a cellular layer in vitro can be subjected to steady and
pulsatile flows in flow chambers. Hemodynamic forces develop a stress field onto
and within the vascular wall, e.g., shear on the wetted surface and intramural stretch.
The stress field acts permanently on vascular cells to modulate gene expression and
release of newly and/or stored substances. In particular, vascular endothelia react to
applied mechanical forces by gene expression.

9.10.6.1 Kr uppel-like Factor-2

In addition to hemodynamic stresses, gene expression can be generated by many
other agents, such as tumor-necrosis factor-

α (TNFSF1) that may involve reactive

oxygen species, interleukin-1 , vascular endothelial

growth factor, among others. These reactions that are not specific to flow, belong to
general adaptive responses.
Nonetheless, the endothelial transcription factor Kr uppel-like factor-2 is
uniquely stimulated by flow [ 1125 ]. Kr uppel-like factor-2 regulates several genes

β , transforming growth factor- β

172 IK channels localize to endothelial projections, where about 40% of TRPV4 reside and
myoendothelial gap junctions are concentrated.