Chapter 12
oxide, there is little basal secretion of PGI
, but secretion can
increase markedly in response to various inputs. The roles of
in the vascular responses to blood clotting are described
in Section F of this chapter.
One of the important
paracrine agents that
the endothelial cells release in response to certain mechanical
and chemical stimuli is
endothelin-1 (ET-1).
ET-1 is a mem-
ber of the endothelin family of peptide paracrine agents secreted
by a variety of cells in diverse tissues and organs, including the
brain, kidneys, and lungs. Not only does ET-1 function as a
paracrine agent, but under certain circumstances it can also
achieve high enough concentrations in the blood to function as
a hormone, causing widespread arteriolar vasoconstriction.
This discussion has so far focused only on arterioles.
However, endothelial cells in arteries can also secrete various
paracrine agents that infl uence the arteries’ smooth muscle,
and thus, their diameters and resistances to fl ow. The force
the fl owing blood exerts on the inner surface of the arterial
wall (the endothelial cells) is called
shear stress;
it increases
as the blood fl
ow through the vessel increases. In response to
this increased shear stress, arterial endothelium releases PGI
increased amounts of nitric oxide, and less ET-1.These agents
cause the arterial vascular smooth muscle to relax and the artery
to dilate. This
ow-induced arterial vasodilation
should be distinguished from
fl ow autoregulation)
may be important in remodeling the arteries and in optimizing
the blood supply to tissues under certain conditions.
Arteriolar Control in Specifi
c Organs
Figure 12–36
summarizes the factors that determine arterio-
lar radius. The importance of local and refl ex controls varies
from organ to organ, and
Table 12–5
lists for reference the
key features of arteriolar control in specifi c organs.
As mentioned at the beginning of Section A, at any given
moment, approximately 5 percent of the total circulating blood
is fl owing through the capillaries. It is this 5 percent that is
performing the ultimate function of the entire cardiovascular
system—the exchange of nutrients, metabolic end products,
and cell secretions. Some exchange also occurs in the venules,
which can be viewed as extensions of capillaries.
The capillaries permeate almost every tissue of the body.
Because most cells are no more than 0.1 mm (only a few cell
widths) from a capillary, diffusion distances are very small,
and exchange is highly effi cient. There are an estimated 25,000
miles of capillaries in an adult, each individual capillary being
only about 1 mm long with an inner diameter of 5 μm, just
wide enough for an erythrocyte to squeeze through. (For
comparison, a human hair is about 100 μm in diameter.)
The essential role of capillaries in tissue function has
stimulated many questions concerning how capillaries develop
and grow
For example, what activates angio-
genesis during wound healing and how do cancers stimulate
growth of the new capillaries required for continued cancer
growth? It is known that the vascular endothelial cells play
a central role in the building of a new capillary network by
cell locomotion and cell division. They are stimulated to do so
by a variety of
angiogenic factors
(e.g., vascular endothelial
growth factor [VEGF]) secreted locally by various tissue cells
like fi broblasts, and by the endothelial cells themselves. Cancer
cells also secrete angiogenic factors. The development of drugs
to interfere with the secretion or action of these factors is a
promising research area in anticancer therapy. For example,
is a substance that inhibits blood vessel growth
and has been found to reduce the size of almost any tumor (or
Arteriolar smooth muscle
Altered arteriolar radius
Hormonal controls
Angiotensin II
Atrial natriuretic
Neural controls
Sympathetic nerves
that release
Neurons that release
nitric oxide
Local controls
Internal blood pressure
(myogenic response)
, CO
, H
Substances released
during injury
Nitric oxide
Figure 12–36
Major factors affecting arteriolar radius. Note that epinephrine can be a vasodilator or vasoconstrictor, depending on which adrenergic receptor
subtype is present.
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