258 Chapter 9
activity increases (during more intense exercise). A reverse
of this antagonism is seen in the digestive tract, where sym-
pathetic nerves inhibit and parasympathetic nerves stimulate
intestinal movements and secretions.
The effects of sympathetic and parasympathetic stimula-
tion on the diameter of the pupil of the eye are analogous to the
reciprocal innervation of flexor and extensor skeletal muscles
by somatic motor neurons (chapter 12, section 12.5). This is
because the iris contains antagonistic muscle layers. Contrac-
tion of the radial muscles, which are innervated by sympathetic
nerves, causes dilation; contraction of the circular muscles,
which are innervated by parasympathetic nerve endings, causes
constriction of the pupils (chapter 10, fig. 10.28).Complementary and Cooperative Effects
The effects of sympathetic and parasympathetic nerves are
generally antagonistic; in a few cases, however, they can be
complementary or cooperative. The effects are complementary
when sympathetic and parasympathetic stimulation produce
similar effects. The effects are cooperative when sympathetic
and parasympathetic stimulation produce different effects that
work together to promote a single action.
The effects of sympathetic and parasympathetic stimula-
tion on salivary gland secretion are complementary. The secre-
tion of watery saliva is stimulated by parasympathetic nerves,
which also stimulate the secretion of other exocrine glands in
the digestive tract. Sympathetic nerves stimulate the constric-
tion of blood vessels throughout the digestive tract. The resul-
tant decrease in blood flow to the salivary glands causes the
production of a thicker, more viscous saliva.
The effects of sympathetic and parasympathetic stimula-
tion on the reproductive system are cooperative. Erection of
the penis, for example, is due to vasodilation resulting from
parasympathetic nerve stimulation; ejaculation is due to stim-
ulation through sympathetic nerves. The two divisions of the
autonomic system thus cooperate to enable sexual function
in the male. They also cooperate in the female; clitoral erec-
tion and vaginal secretions are stimulated by parasympathetic
nerves, whereas orgasm is a sympathetic nerve response, as it
is in the male.
There is also cooperation between the two divisions in the
micturition (urination) reflex. Although the contraction of the
urinary bladder is largely independent of nerve stimulation, it
is promoted in part by the action of parasympathetic nerves.
This is exploited clinically in helping people with inconti-
nence (involuntary urination) caused by overactive bladder. In
this condition, contractions of the detrusor muscle (of the uri-
nary bladder; chapter 17, section 17.1) are stimulated by ACh
released by parasympathetic axons. Newer drugs ( darifenacin
and solifenacin ) are available to block the specific muscarinic
receptor subtypes (primarily M 3 ) that mediate the parasympa-
thetic stimulation of bladder contractions.
The control of micturition requires cooperation with the
sympathetic division, which has antagonistic effects to thenoncholinergic fibers.” Proposed neurotransmitters for these
axons include ATP, a polypeptide called vasoactive intestinal
peptide (VIP), and nitric oxide (NO).
The nonadrenergic, noncholinergic parasympathetic axons
that innervate the blood vessels of the penis cause the smooth
muscles of these vessels to relax, thereby producing vasodilation
and a consequent erection of the penis (chapter 20, fig. 20.21).
These parasympathetic axons have been shown to use the gas
nitric oxide (chapter 7, section 7.6) as their neurotransmitter. In
a similar manner, nitric oxide appears to function as the auto-
nomic neurotransmitter that causes vasodilation of cerebral
arteries. Studies suggest that nitric oxide is not stored in synaptic
vesicles, as are other neurotransmitters, but instead is produced
immediately when Ca^2 1 enters the axon terminal in response
to action potentials. This Ca^2 1 indirectly activates nitric oxide
synthetase, the enzyme that forms nitric oxide from the amino
acid l-arginine. Nitric oxide then diffuses across the synap-
tic cleft and promotes relaxation of the postsynaptic smooth
muscle cells.
Nitric oxide can produce relaxation of smooth muscles
in many organs, including the stomach, small intestine, large
intestine, and urinary bladder. There is some controversy,
however, about whether the nitric oxide functions as a neu-
rotransmitter in each case. It has been argued that, in some
cases, nitric oxide could be produced in the organ itself in
response to autonomic stimulation. The fact that different tis-
sues, such as the endothelium of blood vessels, can produce
nitric oxide lends support to this argument. Indeed, nitric
oxide is a member of a class of local tissue regulatory mol-
ecules called paracrine regulators (chapter 11, section 11.7).
Regulation can therefore be a complex process involving the
interacting effects of different neurotransmitters, hormones,
and paracrine regulators.
Organs with Dual Innervation
Most visceral organs receive dual innervation —they are
innervated by both sympathetic and parasympathetic fibers. In
this condition, the effects of the two divisions of the autonomic
system may be antagonistic, complementary, or cooperative
( table 9.7 ).
Antagonistic Effects
The effects of sympathetic and parasympathetic innervation
of the pacemaker region of the heart is the best example of
the antagonism of these two systems. In this case, sympa-
thetic and parasympathetic fibers innervate the same cells.
Adrenergic stimulation from sympathetic fibers increases the
heart rate, whereas the release of acetylcholine from para-
sympathetic fibers decreases the heart rate. The heart rate is
thereby increased when (1) sympathetic nerve activity remains
constant and parasympathetic activity decreases (the level of
parasympathetic activity most affects the resting heart rate
and early increases in heart rate); and (2) sympathetic nerve