Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 464

Two types of Ca 2 + signals can cause the opening of IK Ca channels in
myoendothelial projections [ 858 ]. Opening of TRPV4 channels on endothelial
membrane causes localized Ca 2 + influxes — Ca 2 + sparklets — that activate
IK Ca and SK Ca channels. This mechanism ensures response to acetylcholine, at
least in mouse small mesenteric arteries. On the other hand, Ca 2 + pulsars caused by
the opening of clusters of IP 3 receptors on parts of the endoplasmic reticulum within
the myoendothelial projections may be generated mainly in these microdomains.
Calcium pulsars can be triggered by IP 3 entering myoendothelial projections
from either the endothelial or smooth myocyte cytosol. The former contributes
to endothelium-dependent hyperpolarization; the latter to the myoendothelial
feedback , by which smooth myocyte contraction is autolimited via K + efflux
from the myoendothelial projection, i.e., by which stimulation of vascular smooth
myocytes activates endothelial cells to repress vasoconstriction.
In addition, calcium wavelets, another IP 3 -dependent endothelial Ca 2 + signal,
play an important role in myoendothelial feedback [ 858 ].
Several types of transient receptor potential channels may be involved in calcium
entry and myoendothelial signaling: in rat cerebral artery, type-1 TRP ankyrin
(TRPA1) and type-3 and -4 TRP vanilloid (TRPV3 and TRPV4) channels; in rat
carotid artery, endothelial TRPV4 channel can trigger NO-dependent relaxation as
well as, in rat gracilis muscle arterioles and in mouse mesenteric artery, both NO-
and EDH-mediated dilation.
Myoendothelial projections are capable of generating localized Ca 2 + pulsars
via non-selective cation channel TRPC3, which lodges on the endothelial plasma
membrane, in close proximity to both IP 3 R on the sarcoplasmic reticulum and
IK Ca on the plasma membrane as well as gap junction, but not on that of vascular
smooth myocytes, at least in rat mesenteric artery [ 861 ]. 16 This channel mainly
localizes to myoendothelial projections. Protein TRPC3 is distributed throughout
the endothelium, but with approximately 5-fold higher density at myoendothelial
contact sites. The K Ca -mediated endothelial-based vasodilation relies on TRPC3
channels [ 861 ].

9.1.3 Vascular Permeability

Angiogenic activity of VEGFa is mainly exerted by upregulating expression of
testicular receptor TR3, or NR4a1 nuclear receptor, in vascular endothelial cells.
Transcription factor NR4a1 contributes to the regulation of vascular permeability in
3 contexts [ 862 ]: (1) basal vascular permeability that suffices to bring nutrients to

16 A spatial and functional association between TRPC3, IP 3 R, and K Ca channels exists in various
cell types (vascular endothelial and smooth muscle cells, pancreatic

β

cells, gastric smooth muscle

cells, etc.).