Download Brain Stem Catecholamine Mechanisms in Tonic and

Brain Stem Catecholamine Mechanisms in Tonic
and Reflex Control of Blood Pressure
DONALD
J.
REIS, ANTONIO
R.
GRANATA, TONG
H.
JOH, CHRISTOPHER
DAVID A. RUGGIERO, AND DONG H.
A. Ross,
PARK
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SUMMARY Neurons of the lower brain stem maintain resting levels of arterial pressure (AP),
mediate reflex responses from cardiopulmonary receptors, and are an important site of the hypotensive actions of a2-adrenergic agonists. Details of the pathways and transmitters that mediate tonic and
reflex control of AP are emerging. Afferent fibers of cardiopulmonary receptors in the ninth and tenth
nerves terminate bilaterally in the nucleus of the tractus solitarius (NTS). Although some neurons
contain substance P, the primary neurotransmitter appears to be the excitatory amino acid L-glutamate (L-glu). Neurons in rostral ventrolateral medulla, which most probably comprise the Cl group
of epinephrine neurons, are also critical in AP control. Cl neurons project to innervate cholinergic
preganglionic sympathetic neurons in the spinal cord. Stimulation of the Cl area electrically or with
L-glu increases AP, while lesions or local injection of the inhibitory amino acid gamma-aminobutyric
acid (GABA) lowers AP to levels comparable to spinal cord transection. Lesions of Cl neurons or their
pathways abolish vasodepressor reflexes from baroreceptors and vagal afferents. In contrast, noradrenergic neurons of the caudal ventrolateral medulla, the Al group, project rostrally to innervate, in
part, vasopressin neurons of the hypothalamus. Stimulation of Al neurons lowers AP, while lesions or
GABA elevates it. We propose that Cl neurons comprise the so-called tonic vasomotor center of the
brain stem and also mediate, via a projection from the NTS, the vasodepressor limb of baroreflexes.
The NTS-C1 projection may be GABAergic. (Hypertension 6 (Suppl II): II-7-II-15, 1984)
KEY WORDS • adrenergic • adrenaline neurons • noradrenergic neurons
baroreceptor reflexes • blood pressure * nucleus of the tractus solitarius
I
T has long been recognized that neurons within the
lower brain stem, which comprise the medulla
oblongata and pons, are critical for the tonic and
reflex regulation of systemic arterial pressure (AP).1"3
Neurons in the lower brain: (1) maintain tonic background drive to sympathetic preganglionic neurons,
thereby maintaining normal resting levels of AP2"4; (2)
are the site of termination of cardiopulmonary afferents, which includes those from high and low pressure
baro- and other cardiopulmonary receptors5"8; and (3)
are the major targets of those centrally acting a-adrenergic agonists that act as antihypertensive agents, most
notably, clonidine and a-methyldopa.9"12 Indeed that
these agents, which act on receptors in the brain normally stimulated by catecholamines, produce cardiovascular actions by stimulation of baroreceptors," n
raises questions about the relationship between the
central networks responsible for maintaining AP and
the central catecholamine neurons.
This paper reviews recent research from our laboratory directed toward clarifying the networks in the
lower brain stem that are responsible for maintaining
normal levels of AP and mediating barorefiex responses. Our findings suggest an important new role
for catecholamine cell groups of the lower medulla in
such control. We review these studies with the present
knowledge of control of the circulation by the brain
stem.
Nucleus of the Tractus Solitarius
and Arterial Pressure
The nucleus of the tractus solitarius (NTS) is the
major site of termination of afferents of the ninth and
tenth cranial nerves. As such, the NTS is the major
relay nucleus for information arising from baroreceptors and cardiopulmonary afferents.
Interestingly, recognition that the NTS is critical for
baroreceptor reflex function is relatively recent and has
From the Laboratory of Neurobiology, Department of Neurology, Cornell University Medical College, 1300 York Avenue, New
York, New York 10021.
Address for reprints: A. R. Granata, Lab. of Neurobiology, 411
E. 69th St., New York, New York 10021.
1-7
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HYPERTENSION SUPPL II VOL 6, No5, SEPTEMBER-OCTOBER 1984
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been elaborated on only over the past 20 years. The
evidence for its role in control of AP stems from a
variety of physiological and anatomical studies.5"8 In
brief: (1) The NTS has been demonstrated by retrograde transport techniques to be the site of termination
of afferents that arise from cardiopulmonary receptors.
(2) Neurons in the NTS can be demonstrated to respond monosynaptically to stimulation of baroreceptor
afferents and also to fire in synchrony with the arterial
pulse, which indicates that they are locked into the
baroreceptor reflex chain. (3) Electrical stimulation of
the NTS can, with stimuli of appropriate frequency,
simulate the baroreceptors, while (4) lesions of the
NTS have been demonstrated to abolish cardiopulmonary reflexes.13 Indeed, lesions of the NTS, produced either by destruction of local neurons or by
appropriate drugs, have been shown to result in neurogenic hypertension.14-l5
drugs such as gamma-aminobutyric acid (GABA),
pentobarbital, or clonidine,10 36~38 reduce AP, sometimes to a magnitude comparable to that produced by
spinal cord transection. In contrast, electrical stimulation or local administration of excitatory amino acids
to the region has been observed to elevate AP. 34 Such
evidence suggests the RVL may be responsible for
maintaining tonic levels of AP. The region also may
mediate vasodepressor responses to baroreflex stimulation: baroreflex responses disappear after bilateral
lesions of, or application of kainic acid to, the area.39- ^
Anatomical studies have also supported the view
that the RVL is important in control of AP; evidence is
available that neurons in the RVL project into regions
of the spinal cord that contain preganglionic autonomic
neurons41^3 and that RVL receives projections from
the NTS.44"17
The cardiovascular portions of the NTS are abundantly innervated by inputs from a variety of brain
areas as well as from branches of the ninth and tenth
nerves. These areas include the area postrema, parabrachial nucleus of the pons, various monoamine brain
stem nuclei of pons, paraventricular and lateral hypothalamic nuclei, amygdala, and forebrain.16"18 These
areas contain a wide variety of peptide and monoamine
transmitters.18 The transmitter of the primary afferent
input is uncertain. Studies from this laboratory over the
past several years have demonstrated that the baroreceptor response may be mediated by the excitatory
amino acid L-glutamate19"23 and not by monoaminergic
nor cholinergic inputs,23"27 although these agents may
modulate the response (as may the various peptides
innervating the area). On the other hand, there is histochemical and immunochemical evidence that substance P also is contained in baroreceptor afferent fibers that innervate the NTS. 28 Whether substance P
acts to mediate baroreflex responses or to modulate
them is uncertain, and the results of application of this
drug locally to the NTS have been variable depending
on species and investigators.29"31
Caudal Ventrolateral Medulla
Ventrolateral Medulla and Cardiovascular Control
Although neurons in the NTS relay all information
arising from cardiopulmonary receptors to other centers in the brain, the pathways by which such information is relayed, particularly those that signal an inhibition of vasomotor tone — the hallmark of the
baroreceptor vasodepressor response — until recently
have been unknown. Attention has focused on the ventrolateral medulla as the area of importance in controlling tonic and reflex control of AP. The ventrolateral
medulla can be separated into a rostral zone, the rostral
ventrolateral medulla (RVL), and a caudal zone, the
caudal ventrolateral medulla (CVL), which, as will be
discussed, differ functionally with respect to their activities in regulating the circulation.
Rostral Ventrolateral Medulla
Studies have documented that bilateral lesions of the
RVL,32"34 c o o ling of the area,35 or local application of
The CVL differs from the RVL with respect to its
actions on AP. Electrical or chemical stimulation of
neurons in the region under appropriate conditions
lowered AP,48-49 while lesions of the area resulted in
elevations of AP.49"5' Neurons in the CVL do not project to the spinal cord (see next section). Thus, in
functional terms, the RVL and CVL appear to have
opposite actions on AP. What has not been determined
are the identity of the neurons and their transmitters
within each of these areas that are responsible for the
cardiovascular effects. That it is different sets of catecholamine neurons within these regions that account
for the functional differentiation has been suggested by
some recent studies, largely from this laboratory.
Catecholamine Neurons in Rostral
Ventrolateral Medulla: Cl Group
It has long been known that the areas of the ventrolateral medulla that have functionally been established
as controlling AP contain neurons that synthesize and
release catecholamines. In their pioneering studies,
Dahlstrom and Fuxe52"53 described a group of histofluorescent neurons in the ventrolateral medulla that
were presumed on the basis of their histofluorescence
to contain norepinephrine. These, the Al neurons,
were believed to project to the spinal cord.
It should be emphasized that histofluorescence cannot differentiate, with certainty, between dopamine,
norepinephrine, or epinephrine. It required the introduction of immunocytochemical techniques for the localization of catecholamine biosynthetic enzymes to
provide a tool that could establish which catecholamine a neuron could synthesize. Thus, neurons that
contained only tyrosine hydroxylase had only the capacity for synthesizing dopamine. The presence of tyrosine hydroxylase and dopamine-/3-hydroxylase indicated that the neuron could synthesize norepinephrine,
while the presence of the enzyme phenylethanolamine
N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine, indicated that
such a cell was adrenergic. In 1974 Hokfelt et al., 54
using an antibody to PNMT, discovered that a subpop-
BRAIN STEM CATECHOLAMINE MECHANISMS//?m et al.
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ulation of neurons called the Cl group, which were
situated in the most rostral portion of the Al group,
contained this enzyme. The ventrolateral Al group
therefore was not homogeneous, but consisted of two
parts: a rostral adrenergic Cl group and a caudal noradrenergic Al group with admixing in between."
Further evidence that the Al and Cl neurons differ
has come from examination of their projections. Using
tracer techniques, it has been established that the Al
neurons do not, as first believed, project to the spinal
cord but rather send their axons rostrally, innervating
in large measure magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus—56~58 neurons that synthesize vasopressin and
project into the posterior pituitary. In contrast, a large
population of Cl neurons also send their axons caudally to innervate almost exclusively the intermediolateral column of the spinal cord (Figure I).59"61 Indeed, the major catecholaminergic innervation of the
spinal cord originating in the medulla oblongata is
adrenergic.59
Possible Function of Cl Adrenergic Neurons in the Tonic
Control of AP
It has long been known that electrical stimulation of
the RVL will elicit elevations of AP and heart rate.3
Whether these effects are mediated by the C1 cells in
the RVL, however, remained to be established.
A144
Medulla
II-9
In a recent series of experiments by combining electrical and chemical stimulation techniques along with
careful correlation with the anatomy of neurons staining for PNMT, we 39 - w have demonstrated an extremely tight correlation between the responses elicited from
the Cl area and the distribution of neurons and their
axonal processes, which contain the enzyme PNMT.
In summary, electrical stimulation of the Cl area or
within the axonal pathways elicited a powerful elevation of arterial pressure and heart rate (Figure 2A).
Such stimulation also elicited a release of adrenal medullary catecholamines and arginine vasopressin (AVP)
from the hypofhalamus. The response to electrical
stimulation was dependent on the stimulus frequency
in so far as the response was elicited with frequencies
of more than 2 Hz and reached a maximum at stimulus
frequencies greater than 100 Hz. The response was
graded with respect to the stimulus intensity. The
threshold for the response was less than 15 piAmp at 5
times the threshold that elicited an elevation of AP in
excess of 80 mm Hg. The pressor response to electrical
stimulation of the Cl area was dependent on stimulation of intrinsic neurons as elevations of AP of comparable magnitude could be elicited by the microinjection
of very small amounts of the excitatory amino acid Lglutamate (L-glu) into the area. Because L-glu did not
excite fibers of passage, we concluded that it was excitation of intrinsic neurons in the C1 area that caused the
sympathetic neurons to discharge.
In contrast to the effects of excitation, interference
with the activity of neurons in the Cl area resulted in a
collapse of AP to levels comparable to those produced
by spinal cord transection. Thus, small electrolytic
lesions (Table I),62"63 the introduction of tetrodotoxin
(Figure 2B),60 or the inhibitory amino acid GABA39 all
lowered arterial pressure. The effects of such disturbances were graded: unilateral lesions only produced
partial reductions of AP.62 Comparable reductions of
AP to those produced by lesions in the Cl cell body
area could also be produced by transecting lesions in
the brain stem that affect the fiber bundle stained for
PNMT (unpublished observations).
These experiments therefore suggest that neurons in
the RVL are tonically active and that these neurons are
tonically inhibited by GABA. These studies are entirely consistent with the view that the Cl neurons of the
RVL provide tonic vasomotor tone.
Role of the Cl Area in Baroreceptor Reflexes
FIGURE I. Autoradiographic demonstration of projections
from the Cl region to the intermediolateral column (ILC). 10
= inferior olive; IVN = inferior vestibular nucleus; MVN =
medial vestibular nucleus; NTS = nucleus of the tractus solitarius; PP = nucleus prepositus; RPa = raphe pallidus; STN
= spinal trigeminal nucleus; STT = spinal trigeminal tract.
(From Ross et al.60)
That the RVL participates in baroreceptor reflex
responses has been suggested by two lines of evidence:
(1) Neurons in the RVL have been shown to be innervated by inputs from the NTS44"46; (2) bilateral lesions
of the RVL or the application of drugs to neurons
subadjacent to it3- *° abolished vasodepressor responses
elicited by electrical or natural stimulation of cardiopulmonary afferents (Table 1). Physiological studies,
however, have been interpreted with difficulty because
lesions or drugs may often drop blood pressure to levels below that reached by maximal stimulation of baroreceptors.
11-10
HYPERTENSION SUPPLII VOL6, No5, SEPTEMBER-OCTOBER 1984
PNMT Label
TS
-200
-150
lOOmmHg
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LOSEC triln
FIGURE 2a. Cardiovascular responses elicited from the Cl region in chloralose-anesthetized, paralyzed, artificially ventilated rats. a. A single electrode tract is seen passing through the ventrolateral medulla (right side of
illustration). At each point, the animal was stimulated for 10 seconds with a square-wave pulse of 20 fxAmp, 100
Hz. Note that the pressor responses are highly localized to regions that correspond with the distribution of cells
labeled for phenvlethanolamine N'-methyltransferase (PNMT) at the same level of the brain stem (left side of
illustration).
TETRODOTOXIN
AFTER SPINAL
TRANSECTION
INJECTION
200
MEAN
ARTERIAL
PRESSURE
(mmHgl
) m
0
200
ARTERIAL
PRESSURE 100
(mmHg)
0
600
HEART RATE
400
(beats/mi n)
200
TTX
TTX
lOmin
lOntin
lmin
FIGURE 2b. Cardiovascular responses to bilateral injections of tet rodo toxin (lOpmolellOO nl saline) into the Cl
area. The first injection (TTX), indicated by an arrow on the bottom of chart recording, produced a partial
reduction of AP, while injection into the contralateral side (second arrow) resulted in a collapse of AP to le\'els
comparable to that produced by subsequent spinal cord transeclion. CST = corticospinal tract;
10 = inferior olive; IVN = inferior vestibular nucleus; MVN = medial vestibular nucleus; NA = nucleus
ambiguus; NTSr = nucleus tractus solitarius pars rostralis; PP = nucleus prepositus; RPa = raphe pallidus;
STN = spinal trigeminal nucleus; STT = spinal trigeminal tract; TS = tractus solitarius. (From Ross, et al.60)
BRAIN STEM CATECHOLAMINE MECHANISMS//?m et al.
II-l
TABLE I. Effec ts upon Resting and Reflex Changes in Arterial Pressure and Heart Rate ofLe\ion(s) ofCI Area Alone or Combined with a
Unilateral Lesion of the NTS*
Before lesion
After lesion
Vagal stimulation
Vagal stimulation
(mean change)
(mean change)
Control
Control
Treatment
Bilateral Cl area lesions
HR
MAP
HR
MAP
HR
380.8
±30.2
-32.5
±3.1
-50 5
±5.0
50.5
±5.0t
220.5
±20.6t
-1.3
±1 0*
-1.5
±1.1*
-36 2
368.0
96.9
±15.2
±6.6
±2.5
By permission of the American Heart Association
-29.8
±5.4
89.4
±7 1
399.6
±26.9
-2.2
±1.0*
-1.8
±0.8*
Contralateral NTS and ipsilateral
Cl area lesions
N
MAP
4
98.5
±8.2
4
MAP
HR
*From Granata et al.62
+p < 0 025.
%p < 0.01. when compared with controls (before lesion).
NOTES: Unilateral vagal stimulation performed with pulse of 2-msec duration. 5 Hz and 10 times threshold current intensity; 10-sec train of
stimulus.
Values are expressed as means ± SEM, N = number of experiments. MAP = mean arterial pressure (mm Hg), HR = heart rate (beats/min);
NTS = nucleus of the tractus solitarius.
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That the Cl neurons of the RVL may mediate the
baroreflex response was suggested to us by our finding
that the Cl area was heavily innervated, largely unilaterally, by a projection of the cardiovascular portions of
the NTS.64 To test the hypothesis that the NTS-C1
projection mediates the vasodepressor response from
baroreceptor afferents, we devised an experimental
model. The model has been based on the facts that the
projections from cardiopulmonary afferents of the
ninth and tenth nerves are distributed bilaterally8; that
the projection from NTS appears primarily unilateral64;
and that lesions of a single Cl area only partially reduce resting AP (unpublished observations). We therefore used a preparation in which the left vagus nerve is
transected and stimulated electrically, and a lesion is
placed in the right NTS, thereby isolating the reflex arc
from the vagal afferents or carotid sinus afferents on
that side to a single loop of the left NTS-left Cl area.
A lesion then placed in the left Cl area should totally
interfere with the reflex arc, but as the right Cl area
remains undamaged, background arterial pressure
should be maintained. Conversely, a lesion of the right
Cl area would have no effect on reflex responses as the
afferent loop of information from the left vagus and
carotid sinus nerves innervating the right Cl has been
interrupted by the unilateral lesion of the right NTS.
We have discovered that (1) lesions of the right NTS
resulted in a slight elevation of resting AP and in partial interference with the magnitude of the vasodepressor response to electrical stimulation of the left vagus
nerve or stretch of the left carotid sinus region; (2) the
addition of a lesion of either the right or left Cl area
resulted in a lowering of AP to a level comparable to
that in the unoperated anesthetized rat (Table 1); (3) a
lesion of the left Cl area totally abolished reflex responses elicited by electrical stimulation of the left
vagus nerve (Table 1) or carotid sinus (Table 2); (4)
electrolytic lesion of the right NTS combined with a
lesion of the right Cl area had no further effect on
vasodepressor responses than did the NTS lesion
alone; (5) if kainic acid was injected into the left Cl
area rather than placement of an electrolytic lesion, a
TABLE 2. Effects upon Cardiovascular Responses to Carotid Sinus Stretch of Le.sion(s) ofCI Area Alone or Combined with a Unilateral
Lesion of the NTS*
After lesion
Before lesion
Carotid sinus stretch
(mean change)
Control
Treatment
N
Bilateral Cl area lesions
4
Contralateral NTS and ipsilateral
Cl area lesions
5
HR
MAP
HR
98.9
±8.5
346
±20.8
-27.8
±6.1
-27.2
±7.1
95.8
±10.5
355.0
±10.1
-29.8
±6.7
-30.5
±7.5
MAP
Carotid sinus stretch
(mean change)
Control
HR
HR
MAP
51.01±8.1
233.3t
±25.0
-1.5*
±1.3
- 1 8*
± 1.4
89.9
±7.5
340.5
±16.0
-1.8
±1.1*
- 1.5
±1.1*
MAP
*From Granata et al. 62
tp < 0.025.
*p < 0.01 when compared with controls (before lesion).
NOTES: The carotid sinus baroreceptors were stimulated naturally (stretched) by pulling the ligature looped around the common carotid
artery downward toward the heart for 12 sec. In all cases, ipsilateral and contralateral are referred to the side of the vagal stimulation or carotid
sinus stretch.
Values are expressed as mean ± SEM; N = number of experiments; MAP = mean arterial pressure (mm Hg); HR = heart rate (beats/min);
NTS = nucleus of the tractus solitarius.
HYPERTENSION
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SUPPLII V O L 6 ,
comparable abolition of baroreceptors was obtained,
which indicated that the effects of electrolytic lesions
are on neurons in the region rather than on fibers of
passage.63 Most recently we have obtained evidence
that lesions restricted to the axonal bundles of PNMTcontaining fibers that project dorsally and then descend
into the spinal cord produce effects comparable to
those obtained with electrolytic lesions of the cell
bodies (unpublished observations).
These observations raise the question as to whether
or not Cl neurons may be important in the expression
of several forms of hypertension. That a unilateral Cl
lesion reduced the significant elevation of arterial pressure produced by NTS lesions, demonstrates that its
integrity is necessary for the expression of at least the
neurogenic hypertension produced by bilateral lesions
of the NTS (NTS hypertension).
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Contrasting Roles of A l Neurons of the Caudal
Ventrolateral Medulla in Cardiovascular Function
Electrical stimulation of the A1 area in the rabbit48 or
49
rat resulted in changes of AP that were very different
from those elicited from the Cl area. Electrical stimulation of the region with low-frequency stimuli (5-15
Hz) or the microinjection of the excitatory amino acid
L-glu resulted in graded reductions of AP. Electrical
stimulation with higher frequencies resulted in a pressor response. In the rabbit the vasodepressor response
was accompanied by bradycardia; in the rat, by tachycardia.
No 5, SEPTEMBER-OCTOBER 1984
Lesions of the Al area produced effects entirely
different from that produced by lesions of the Cl area.
Thus, electrolytic lesions or the introduction of kainic
acid into the Al area of rabbit50"51 or rat49 resulted in
elevations of AP, which led inevitably in the rat and
often in the rabbit, to fulminating pulmonary edema
and death. The microinjection of GAB A into the Al
area also resulted in an elevation of arterial pressure.48
Lesions of the Al area, in contrast to those of the Cl
area, did not substantially alter the magnitude of the
vasodepressor response to maximal stimulation of vagal afferent fibers or to carotid sinus stretch.49 Chronically, lesions of the A1 area, however, may impair the
gain of the baroreceptor reflex curve.50
The hypertension produced by Al lesions was substantially, but not totally, the result of an increase in
the release of AVP from the pituitary.49"50 Thus, interference with Al function by electrolytic lesions or
kainic acid elevated AP, and the response to hypertension was significantly reduced by treatment with an
AVP antagonist.
The Neuroanatomical Substrate of the Tonic and
Baroreceptor Reflex Control
From these considerations and previous work from
our laboratory, we constructed a working diagram of
the neuroanatomy of the baroreceptor reflex arc (Figure 3). In brief, afferent information arising from baroreceptors projects into the NTS. From here it engages
neurons that project to the Cl area; Cl neurons project
Primary afferents
(Glu)
FIGURE 3.
Medulla
Carotid
sinus
Thoracic cord
Preganglionic
sympathetic
neuron (Ach)
Heart
Adrenal medulla
Postganglionic
sympathetic
neuron (NE)
Diagrammatic representa-
tion of proposed pathways and neurotransmitters that mediate baroreceptor
reflex activity. Afferent fibers of the
ninth (IX) and tenth (X) nerves terminate in the nucleus of the tractus solitarius (NTS) with a proposed neurotransmitter being L-glutamate (Glu). Here
they synapse on neurons that relay into
the Cl area. The transmitter of these
neurons may be gamma-aminobutyric
acid (GABA). These neurons, which
synthesize epinephrine (E), innervate
cholinergic neurons in the intermediolateral (IML) and inter mediomedial levels of the spinal cord, which then relay
either into the adrenal medulla or into
sympathetic ganglion where they contact noradrenergic postganglionic neurons, which in turn innervate noradrenergic sympathetic neurons (NE), which
innervate blood vessels, the heart, or
both. Also shown are neurons in the
dorsal motor nucleus (DMX) of the \<agus and in the nucleus of Nosaka (N),
which provide efferent innervation of
the heart and nucleus ambiguus (NA).
BRAIN STEM CATECHOLAMINE MECHANISMS//?m et al.
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into the intermediolateral column of the cord, with
neurons of that region projecting directly to the adrenal
medulla or to sympathetic ganglia, which make contact with those ganglionic neurons that innervate the
blood vessels and the heart.
A provisional statement can be made about the neurochemistry of this loop. The neurotransmitter of the
primary afferent fibers is still not completely established. As described previously, there is substantial
evidence to suggest that these fibers may contain L-glu
and that the release of this amino acid transmits information from baroreceptors onto neurons of the NTS.
Because, however, afferent fibers contain substance P,
they may exert some yet unknown function on the
reflex response.
The transmitter of the NTS-C1 projection is not
yet clearly established; however, the abundant evidence66"67 that (1) GAB A is essential in mediating
baroreceptor reflex responses on heart rate and also on
blood pressure, (2) the site of action seems to be in the
ventrolateral medulla, and (3) neurons in the NTS will
release GABA in vitro (Meeley MP, Reis DJ, unpublished observation), makes this a reasonable candidate
for this limb of the reflex arc.
Excitation of the Cl area was necessary to mediate the tonic vasomotor and reflex vasodepressor responses, and hence the transmitter in this limb could be
epinephrine. Whether or not it is epinephrine that is
released to act on preganglionic neurons in the spinal
cord to lower arterial pressure remains to be established. That the microiontophoresis of epinephrine in
the area of preganglionic neurons purportedly reduces
their activity rather than elevates it is a perplexing
paradox.68"*9 That Cl neurons have been discovered to
contain other neuropeptides, however, such as neuropeptide Y,70 raises the possibility that the release of
some agent other than epinephrine may produce the
effect. The transmitter from the preganglionic sympathetic neuron to the ganglion cells is presumably acetylcholine, although these neurons may contain cotransmitters, and finally, the effective transmitter
released from noradrenergic neurons on blood pressure
is norepinephrine.
We must emphasize that the neurochemical wiring
diagram of the baroreceptor reflex arc acting on blood
pressure is provisional and a working hypothesis. Sufficient surprises have emerged from studies of neurotransmitter systems over the last decade to make
enthusiastic statements premature in identifying transmitters).
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Brain stem catecholamine mechanisms in tonic and reflex control of blood pressure.
D J Reis, A R Granata, T H Joh, C A Ross, D A Ruggiero and D H Park
Hypertension. 1984;6:II7
doi: 10.1161/01.HYP.6.5_Pt_2.II7
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