C h a p t e r 1 7
Control of Cardiovascular Function
399
nitric oxide production and vessel relaxation. Nitric
oxide also inhibits platelet aggregation and secretion
of platelet contents, many of which cause vasoconstric-
tion. Nitroglycerin, a drug used in treatment of angina,
produces its effects by releasing nitric oxide in vascular
smooth muscle of the target tissues.
The endothelium also produces a number of vaso-
constrictor substances, including
angiotensin II
, vaso-
constrictor prostaglandins, and a family of peptides
called
endothelins
. There are at least three endothelins.
Endothelin-1 is the most potent endogenous vasocon-
strictor known.
Humoral Control of Blood Flow
Humoral control of blood flow involves the effect of
vasodilator and vasoconstrictor substances in the blood.
Some of these substances are formed by special glands
and transported in the blood throughout the entire cir-
culation. Others are formed in local tissues and aid in
the local control of blood flow. Among the most impor-
tant of the humoral factors are norepinephrine and
epinephrine, angiotensin II, histamine, serotonin, bra-
dykinin, and the prostaglandins.
Norepinephrine and Epinephrine.
Norepinephrine is
an especially powerful vasoconstrictor hormone; epi-
nephrine is less so and in some tissues (e.g., skeletal
muscle) even causes mild vasodilation. Stimulation of
the sympathetic nervous system during stress or exercise
causes local constriction of veins and arterioles due to
the release of norepinephrine from sympathetic nerve
endings. In addition, sympathetic stimulation causes the
adrenal medullae to secrete both norepinephrine and
epinephrine into the blood. These hormones then circu-
late in the blood, causing direct sympathetic stimulation
of blood vessels in all parts of the body.
Angiotensin II.
Angiotensin II, another powerful
vasoconstrictor, is produced as a part of the renin-angiotensin-aldosterone system. It normally acts on
many arterioles at the same time to increase the periph-
eral vascular resistance, thereby increasing the arterial
blood pressure (discussed in Chapter 18).
Histamine.
Histamine has a powerful vasodilator
effect on arterioles and has the ability to increase cap-
illary permeability, allowing leakage of both fluid and
plasma proteins into the tissues. Histamine is largely
derived from mast cells in injured tissues and basophils
in the blood. In certain tissues, such as skeletal muscle,
the activity of the mast cells is mediated by the sym-
pathetic nervous system; when sympathetic control is
withdrawn, the mast cells release histamine.
Serotonin.
Serotonin, which is liberated from aggregat-
ing platelets during the clotting process, causes vasocon-
striction and plays a major role in control of bleeding.
Serotonin is found in brain and lung tissues, and there is
some speculation that it may be involved in the vascular
spasm associated with some allergic pulmonary reac-
tions and migraine headaches.
Bradykinin.
The kinins (i.e., kallidins and bradykinin)
are small polypeptides that are liberated from the glob-
ulin kininogen, which is present in body fluids. They
cause powerful vasodilation when formed in the blood
and tissue fluids of organs. Bradykinin causes intense
dilation of arterioles, increased capillary permeability,
and constriction of venules. It is thought that the kinins
play special roles in regulating blood flow and capillary
leakage in inflamed tissues. It is also believed that brady-
kinin plays a major role in regulating blood flow in the
skin as well in the salivary and gastrointestinal glands.
Prostaglandins.
Prostaglandins are synthesized from
constituents of the cell membrane (i.e., the long-chain
fatty acid
arachidonic acid
). Tissue injury incites the
release of arachidonic acid from the cell membrane,
which initiates prostaglandin synthesis (see Chapter 3,
Fig. 3-4). There are several prostaglandins (e.g., E2, F2,
D2), which are subgrouped according to their solubility;
some produce vasoconstriction and some produce vaso-
dilation. As a general rule, those in the E group are vaso-
dilators and those in the F group are vasoconstrictors.
The corticosteroid hormones produce an anti-inflam-
matory response by blocking the release of arachidonic
acid, thereby preventing prostaglandin synthesis.
Collateral Circulation
Collateral circulation is a mechanism for the long-term
regulation of local blood flow. In the heart and other
vital structures, anastomotic channels exist between
some of the smaller arteries. These channels permit per-
fusion of an area by more than one artery. When one
artery becomes occluded, these anastomotic channels
increase in size, allowing blood from a patent artery to
perfuse the area supplied by the occluded vessel. For
example, persons with extensive obstruction of a coro-
nary blood vessel may rely on collateral circulation to
meet the oxygen needs of the myocardial tissue normally
supplied by that vessel. As with other long-term com-
pensatory mechanisms, the recruitment of collateral cir-
culation is most efficient when the obstruction to flow is
gradual, rather than sudden.
Neural Control of Blood Flow
The neural control of the circulation occurs primar-
ily through the
sympathetic
and
parasympathetic
divi-
sions of the autonomic nervous system (ANS). The
ANS contributes to the control of cardiovascular func-
tion through modulation of cardiac function (i.e., heart
rate and cardiac contractility) and peripheral vascular
resistance.
The neural control centers for the integration and
modulation of cardiac function and blood pressure are
located bilaterally in the medulla oblongata of the brain.
The medullary cardiovascular neurons are grouped into
three distinct pools that lead to sympathetic innerva-
tion of the heart and blood vessels and parasympathetic
innervation of the heart. The first two, which control
