Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 596

shear

ATn2

PoG

I

RTK GPCR NOx

Ca

EC

Rho

PI3K

Cam

PKC ERK stretch

NO

Csk

Cam/CamK

ET

Cam/PP2B

NFAT

stretch

TNF α

TGF β

ATn2

PDGF

I

GCase RTK GPCR NOx

SMC

DAG

Ca

IP3

PI3K

Rho MMP

PKC

(VD) (VC)

Ca

Csk

MAPK

Csk

PKB

growth

Fig. 9.12 Artery wall adaptation to hemodynamic stresses. The artery bore is locally controlled
by mechanotransduction experienced by both endothelial and smooth muscle cells as well as
hormones and growth factors. Angiotensin-2 acts on endothelial cells via NO to cause vasodilation
that reduces vasoconstriction generated by direct angiotensin-2 effect on smooth myocytes. In
other words, angiotensin-2 receptors have opposite effects according to cell type. Their number on
endothelial cells is smaller than that on smooth myocytes (I: integrin; PoG: proteoglycan; NOx:
reduced form of nicotine adenine dinucleotide phosphate (NAD(P)H) oxidase; NFAT: nuclear
factor of activated T cells).

A fundamental couple at the microscopic scale is composed of an endothelial
and a smooth muscle cell (Fig. 9.13 ). At the nanoscopic scale, numerous agents
contribute to the local control of the vasomotor tone (Table 9.34 ). Yet, let us
consider a fundamental couple at the nanoscopic scale: nitric oxide and endothelin
that cause vasodilation and -constriction, respectively. The major regulators of the
vasomotor tone are thus assumed to carry out the entire chemical control. Even
using this assumption, reality remains complex. Endothelin-1 indeed targets 2 types
of cognate receptors — ET A and ET B — that have opposite effects (Table 9.35 ).
The simplified model of mechanotransduction takes into account these 2 types of
endothelin receptors to be representative enough (Fig. 9.14 ).