CHAPTER 3 • CELLULAR STRUCTURE AND FUNCTION
5 5
In addition, endothelial cells synthesize
endothelin-1 (ET-1), a powerful vasoconstric-
tor (see Fig. 3.11). Synthesis is stimulated
by angiotensin II, vasopressin,
thrombin,
cytokines, and shearing forces, and it is inhib-
ited by NO and PGIr ET-1 leaves the endothe-
lial cell and can bind to receptors (ETA) on
vascular smooth muscle, which causes cal-
cium mobilization and smooth muscle con-
traction. The smooth muscle actions of ET-1
occur through activation of the IP3 signaling
pathway (see Fig. 3.10).
PGI2 is a product of arachidonic acid
metabolism within endothelial cells. The two
primary roles of PGI2 formed by endothelial
cells are smooth muscle relaxation and inhi-
bition of platelet aggregation (see Fig. 3.11),
both of which are induced by the formation of
cAMP (see Fig. 3.10).
The importance of normal endothelial
function is made clear from examining how
endothelial dysfunction contributes to dis-
ease states. For example, endothelial dam-
age and dysfunction occur in atherosclerosis,
hypertension, diabetes, and hypercholester-
olemia. Endothelial dysfunction results in
less NO and PGI2 production, which causes
vasoconstriction, loss of vasodilatory capacity,
thrombosis, and vascular inflammation. Evi-
dence exists that enhanced ET-1 production
contributes to hypertension and other vascu-
lar disorders. Physical damage to the endothe-
lium at the capillary level increases capillary
permeability (see Chapter 8), which leads to
increased capillary fluid filtration and tissue
edema.
PROBLEM 3-3
When acetylcholine is infused
into normal coronary arteries, the
vessels dilate; however, if the vessel
is diseased and the endothelium
damaged, acetylcholine can cause
vasoconstriction. Explain why
acetylcholine can have opposite effects
on vascular function depending on the
integrity of the vascular endothelium.
SUMMARY OF IMPORTANT CONCEPTS
ATP, which is generated primarily by
oxidative metabolism of fatty acids and
carbohydrates, although the heart is
flexible in its use of substrates and can
also metabolize amino acids, ketones,
and lactate.
*
The basic contractile unit of a cardiac
myocyte is the sarcomere, which
contains thick filaments (myosin) and
thin filaments (actin, troponin, and
tropomyosin) that are involved in
muscle contraction.
*
Excitation-contraction coupling is
initiated by depolarization of the
cardiac myocyte, and is controlled
by changes in intracellular calcium,
which binds to regulatory proteins on
the thin filaments; ATP is required for
contraction and relaxation.
*
Relaxation of cardiac myocytes
(lusitropy) is primarily regulated by the
reuptake of calcium into the sarcoplasmic
reticulum by the SERCA pump.
*
The contractile function of cardiac
myocytes requires large amounts of
Arteries and veins are arranged as
three layers: adventitia, media, and
intima. Autonomic nerves and small
blood vessels (vasa vasorum in large
vessels) are found in the adventitia;
vascular smooth muscle is found in the
media; and the intima is lined by the
endothelium.
Vascular smooth muscle contains
actin and myosin; however, these
components are not arranged in the
same repetitive pattern as that found in
cardiac myocytes. Unlike cardiac muscle
(
Continued
)
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