Abstract : Airway dilation is one of
the many autonomic responses to exercise. Two
neural mechanisms are believed to evoke these
responses: central command and the muscle
reflex. Previously, we found that activation of
central command, evoked by electrical and
chemical stimulation of the mesencephalic
locomotor region, constricted the airways rather
than dilated them. In the present study we
examined in decerebrate paralyzed cats the role
played by the hypothalamic locomotor region, the
activation of which also evokes central command,
in causing the airway dilator response to
exercise. We found that activation of the
hypothalamic locomotor region by electrical and
chemical stimuli evoked fictive locomotion and,
for the most part, airway constriction. Fictive
locomotion also occurred spontaneously, and this
too, for the most part, was accompanied by
airway constriction. We conclude that central
command plays a minor role in the airway dilator
response to exercise.
Dynamic exercise evokes a large number of
cardiovascularand respiratory responses, one of
which is airway dilation. The neural mechanism
responsible for the exercise-induced airway
dilation is not known, but central command is an
important candidate and is defined as the
parallel activation of locomotor, ventilatory,
and autonomic circuits at the onset of exercise.
Central command is not dependent on feedback
from the periphery.
In animals, central command can be simulated
by activation of two sites: the cuneiform
nucleus of the midbrain and in or near the H2
field of Forel of the posterior hypothalamus.
The former site has been termed the
mesencephalic locomotor region and the latter
the hypothalamic locomotor region (HLR). In a
recent study our laboratory showed that
electrical and chemical stimulation of the
mesencephalic locomotor region increased total
lung resistance,an effect that was caused by the
activation of cholinergic receptors on airway
smooth muscle.
This finding was surprising because it
provided no support for the hypothesis that
central command contributed to the airway
dilation evoked by dynamic exercise. In the
present study we have sought support for this
hypothesis by stimulating the other central
command site, i.e., the HLR. In addition, we
have examined the effect of fictive locomotion,
occurring spontaneously, on airway caliber.
Discussion We have examined the role
of the HLR in the control of airway caliber.
Specifically, we tested the hypothesis that
activation of this region is responsible for the
airway dilation seen during dynamic exercise.
Our requirements for the successful activation
of the HLR, and therefore central command, were
based on functional criteria. These included
increases in mean arterial pressure, increases
in heart rate, increases in phrenic nerve
discharge, and fictive locomotion, each of which
must have occurred for the data to be included
in our analysis. Overall, our data were not
supportive of the hypothesis that the HLR plays
an important role in causing the airway dilation
evoked by dynamic exercise. For example, in 70%
of the 23 cats tested, electrical stimulation of
the HLR constricted the airways. When dilation
of the airways did occur (i.e., in ,30% of
cats), its magnitude was modest. In addition,
the airway constriction evoked by electrical
stimulation did not appear to be an artifact
caused by the activation of fibers of passage,
because the same effect was caused by
microinjection of picrotoxin, a GABA antagonist,
which functions by blocking chloride iontophores
on cell bodies and dendrites.
When stimulation of the HLR did evoke airway
dilation, the response was converted by
b-adrenergic blockade to airway constriction and
subsequently was abolished by atropine. We can
offer two explanations for the mechanism causing
the airway dilator response to HLR stimulation.
First, stimulation of the HLR activated
b-adrenergic receptors located on airway smooth
muscle. This activation could occur by the
release of transmitter from sympathetic
postganglionic nerves or by the release of
epinephrine from the adrenal gland. Second, the
pressor response to HLR stimulation evoked the
baroreflex, one component of which is airway
dilation. We do not know which explanation is
correct, but when airway dilation was evoked by
HLR stimulation, the pressor response was, on
average, 18 mmHg greater than that when airway
constriction was evoked by HLR stimulation. We
speculate that in the seven cats showing a
dilator response to HLR stimulation the large
pressor effect may have been sufficient to
overwhelm the airway constriction usually
observed when this maneuver is initiated.
Nevertheless, electrical stimulation of the
HLR for the most part evoked airway
constriction, as evidenced by an increase in
total lung resistance. This increase was not
effected by b-adrenergic blockade but was
abolished by muscarinic blockade. This finding
is consistent with previous reports that the
constrictor response to stimulation of the brain
stem is caused by the activation of cholinergic
pathways to airway smooth muscle.
If central command is not the major neural
mechanism causing the exercise-induced airway
dilation, then what is? Two candidates come to
mind: the Hering-Breuer reflex and the muscle
reflex. Both evoke bronchodilation by withdrawal
of cholinergic tone to airway smooth muscle.
Slowly adapting stretch receptors comprise the
afferent arm of the Hering-Breuer reflex arc.
The activity of these slowly adapting receptors
will be increased by exerciseinduced increases
in tidal volume and the rate of breathing.
Similarly, group III and IV afferents comprise
the afferent arm of the muscle reflex arc. The
activity of these thin fiber afferents is known
to be increased by dynamic exercise.
Our conclusion that activation of the HLR is
not the major mechanism causing exercise-induced
airway dilation applies to the tracheobronchial
tree but not to the upper airways. In our
experiments the cats were paralyzed, which
prevented neurotransmission from the HLR to the
skeletal muscles. In addition, the trachea was
cannulated below the larynx, which removed the
upper airways from our calculations of total
lung resistance and dynamic compliance.
Consequently, the role of central command in the
control of the upper airways during exercise
remains to be determined.
The fact that the cats used in our
experiments were paralyzed and ventilated had
another consequence; i.e., feedback from
pulmonary stretch receptors to brainstem neurons
controlling airway caliber and breathing was
abnormal. In turn, afferent input from these
receptors reached the brain stem out of phase
with central respiratory drive. Therefore, we
cannot exclude the possibility that this factor
was responsible for our inability to evoke major
dilation of the airways during stimulation of
the HLR. We were, however, able to evoke airway
dilation in our preparation when the tibial
nerve was stimulated electrically (present
results) or when the triceps surae muscles were
contracted statically.
There is no doubt that central command plays
an important role in the control of
cardiovascular and ventilatory function during
exercise. Indeed, central command is thought to
be the dominant mechanism causing the
ventilatory response to exercise).
Nevertheless, central command appears to
play a minor role in the airway smooth muscle
dilation known to occur during dynamic exercise.
This conclusion is based on the assumption that
the hypothalamic and mesencephalic locomotor
regions of the decerebrate unanesthetized cat
comprise the neuroanatomic substrate for central
command. Other sites in the brain stem may also
be involved in the generation of central
command, and their effects on airway caliber
will need to be investigated as these sites are
identified.
