CHAPTER 7 • ORGAN BLOOD FLOW
serving as an inhibitor of platelet aggregation.
PGI2 synthesis is stimulated by adenosine and
nitric oxide, as well as by many other sub-
stances, and therefore can play a secondary
role to the vasodilation produced by other
substances. It causes vasodilation by activat-
ing smooth muscle adenylyl cyclase, which
increases cAMP (see Chapter 3).
Endothelin-1 (ET-1) is a potent vasoconstric-
tor substance that is synthesized from an intra-
enzyme (ECE) found on the endothelial cell
membrane. ET-1 binds to ETA
smooth muscle cells, which are coupled to Gq-
proteins (see Chapter 3). ET-1 can also bind
to a second type of receptor (ETB) located on
the vascular endothelium that stimulates nitric
oxide and prostacyclin synthesis and release,
which act as negative feedback mechanisms to
counteract the ETA-mediated vasoconstrictor
effects of ET-1.
ET-1 formation and release by endothelial
cells is stimulated by angiotensin II, vasopres-
sin (antidiuretic hormone, ADH), thrombin,
cytokines, reactive oxygen species, and shear-
ing forces acting on the vascular endothelium.
ET-1 release is inhibited by nitric oxide, as well
as by prostacyclin and atrial natriuretic peptide.
Some forms of hypertension (e.g., pulmonary
artery hypertension) appear to involve ET-1
and are treated with ET-1 receptor blockers.
Smooth Muscle (Myogenic)
M yogenic m echanisms originate within the
sm ooth m uscle of blood vessels, particu-
larly in small arteries and arterioles. W hen
the lumen of a blood vessel is suddenly
pressure is suddenly increased, the sm ooth
m uscle responds by contracting in order to
restore the vessel diameter and resistance.
pressure results in sm ooth m uscle relaxa-
studies have shown that vascular sm ooth
leading to calcium entry into the cell (pri-
marily through L-type calcium channels),
phosphorylation of m yosin light chains, and
contraction (see Chapter 3).
Myogenic behavior has been observed in
many different vascular beds, although its
relative functional significance differs among
organs. It is difficult to evaluate myogenic
mechanisms in vivo because changes in pres-
sure are usually associated with changes in
flow that trigger metabolic mechanisms, which
usually dominate over myogenic mechanisms.
For example, increasing venous pressure to a
vascular bed should activate myogenic mecha-
nisms to produce vasoconstriction because
elevated venous pressures are transmitted back
to the precapillary resistance vessels; however,
the reduction in blood flow associated with the
increase in venous pressure (which reduces
bolic mechanisms that cause vasodilation. In
most organs, conducting such an experiment
usually results in vasodilation because the
metabolic vasodilator response overrides the
myogenic vasoconstrictor response, if present.
Mechanical compressive forces can affect vas-
cular resistance and blood flow within organs.
Sometimes this occurs during normal physi-
ologic conditions; at other times, compressive
forces can be the result of pathologic mecha-
nisms. The pressure that distends the wall of a
blood vessel is the transmural pressure (inside
minus outside pressure).
Therefore, if the
pressure outside of the vessel increases, then
the transmural pressure decreases. At very
high extravascular pressures, a vessel can com-
pletely collapse. Therefore, veins, which have a
relatively low intravascular pressure, are more
likely to collapse when extravascular pressure
is elevated; however, arteries can also become
significantly compressed when extravascular
pressure is elevated to very high levels.
Several examples of mechanical compres-
sion affecting organ blood flow exist. During
cardiac systole or skeletal muscle contraction
lar resistance is greatly increased and blood
flow is impeded by mechanical compression.
Lung inflation and deflation alter pulmonary