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Departments of Anesthesiology and Physiology, The Medical College of Wisconsin and the Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The role of 5-hydroxytryptamine 1A (5-HT1A) receptors located in the rostral ventrolateral medulla (RVLM) in the mediation of a sympathoinhibitory and depressor response elicited from the ventrolateral periaqueductal gray (vlPAG) matter of the midbrain was examined in pentobarbital sodium-anesthetized rats. Activation of neurons in the vlPAG evoked a decrease in renal and lumbar sympathetic nerve activities and a decrease in arterial blood pressure. After microinjection of the specific 5-HT1A-receptor antagonist WAY-100635 into the pressor area of the RVLM, the vlPAG-evoked sympathoinhibition and hypotension was attenuated to control levels (7 of 15 animals) or converted into a sympathoexcitation and pressor response (8 of 15 animals). Baroreflex inhibition of sympathetic nerve activity was not impaired by microinjection of WAY into the sympathoexcitatory region of the RVLM. These data suggest that sympathoinhibition and hypotension elicited by activation of neurons in the vlPAG are mediated by 5-HT1A receptors in the RVLM.
serotonin; periaqueductal gray matter; rostroventrolateral medulla; sympathetic nerve activity; blood pressure; rat
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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MODULATION OF THE ONGOING activity of sympathoexcitatory neurons located in the rostroventrolateral medulla (RVLM) can establish specific patterns of regional sympathetic nerve activity and produce changes in blood flow and blood pressure. Whereas the phenotype of sympathoexcitatory RVLM neurons has yet to be conclusively characterized, they are considered to be spinally projecting and barosensitive (6, 22). It is estimated that 80-91% of barosensitive RVLM neurons are spinally projecting (15, 30), and most barosensitive RVLM neurons are catecholaminergic, C1 neurons (22, 30, 33). Sympathoinhibition and hypotension can be elicited by microinjection of the 5-HT1A-receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) into the RVLM (1, 11, 21, 29), suggesting that the sympathoinhibition can occur by serotonergic modulation of the activity of sympathoexcitatory RVLM neurons. In support of this hypothesis, immunohistochemical evidence demonstrates the presence of 5-hydroxytryptamine 1A (5-HT1A) receptors on both catecholaminergic and noncatecholaminergic RVLM neurons with projections to the intermediolateral cell column of the spinal cord (16). In addition, electrophysiological studies have demonstrated that the discharge rate of putative sympathoexcitatory neurons in the RVLM can be reduced by local microiontophoresis of 5-HT1A receptor agonists (20, 37) or intravenous administration of 8-OH-DPAT (17, 29).
Tracing techniques indicate that numerous regions provide afferent inputs to the RVLM (34), and serotonergic neurons have been located immunohistochemically in some of these areas, including the ventrolateral periaqueductal gray (vlPAG) matter in the midbrain (3, 5, 31) and the caudal and rostral raphe nuclei (12, 31). Both the vlPAG and the raphe nuclei are thought to be involved in cardiovascular control perhaps via a relay in the RVLM (7, 36, 38). Neurons in the vlPAG have been shown to project to the sympathoexcitatory region of the RVLM (8, 10) and vlPAG neurons have been retrogradely labeled from a region of the RVLM from which a hypotensive response could be evoked (7). Whereas the responses of sympathetic outflows to stimulation of vlPAG neurons have not been examined, the activity of RVLM neurons can be inhibited by electrical stimulation in the vlPAG (37, 39), an effect that may be mediated by an indirect pathway through the raphe (39). Sympathoinhibition that can be evoked from raphe neurons is thought to be mediated in part by raphe-spinal projections (27), but there is evidence for raphe-RVLM projections (9, 28, 34, 36) and axonal collaterals directed to RVLM from raphe-spinal axons (2, 26).
Inhibition of RVLM neuronal discharges by vlPAG stimulation has been shown to be reduced after intravenous administration of the serotonergic receptor antagonist spiperone (37). The present study was performed to determine the responses of regional sympathetic outflows to activation of vlPAG neurons. Furthermore, this study examines the role of RVLM 5-HT1A receptors in the inhibition of sympathetic outflows and the accompanying hypotension elicited from activation of neurons in the vlPAG.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The protocol for this study was approved by the Animal Care and Use Committees of the Medical College of Wisconsin and of the Zablocki Department of Veterans Affairs Center. The experiments were performed in Sprague-Dawley rats (250-350 g) anesthetized with pentobarbital sodium (50 mg/kg ip) with a catheter inserted into a femoral vein for supplemental administration of anesthetic. Arterial blood pressure was monitored continuously from a femoral arterial cannula connected via a pressure transducer (Statham) to a polygraph (Grass model 7) and recorded on tape (Vetter PCM recording adaptor model 3000A). A heating pad was used to maintain body temperature at 37°C. The trachea was cannulated through a midline cervical incision for artificial ventilation (Bird Mark 7 respirator) with 100% O2, if necessary. Blood samples were taken at intervals, and arterial blood gases were maintained within physiological limits by infusion of bicarbonate or adjustment of ventilation.
The head of the animal was fixed in a stereotaxic frame (Kopf), and sympathetic nerve activity was recorded using flexible silver wire electrodes positioned on a renal nerve (n = 7 ) or the lumbar sympathetic nerve (n = 6) via a retroperitoneal approach. In two additional animals, lumbar and renal sympathetic nerve activities were recorded simultaneously. The electrodes were fixed in position with Silastic gel, allowing adjustment of the body of the animal without disturbing neural recordings. The electrophysiological signals were directed to high-impedance differential amplifiers (gain 1,000; 0.1-10 kHz passband), followed by filter/amplifiers (gain up to 400; high- and low-pass filtering 10 Hz-3 kHz) and recorded on tape. The amplifier output was directed to precision full-wave rectifiers and averaged using Bessel linear averaging filters (averaging interval 100 ms) to obtain an online moving time average. The averaged activities were displayed on a Grass model 7 recorder to observe trends during the experiment.
For central microinjections, dorsal craniotomies were performed, and the dura was reflected to allow the insertion of micropipettes. The micropipettes were advanced slowly using a microdrive, and initial coordinates with respect to bregma were (in mm caudal, lateral, and depth, respectively) 7.6, 0.6, and 5.5 for the vlPAG and 11.8, 1.2, and 8.5 for the RVLM, with target sites identified functionally as described below. Multibarreled glass micropipettes (10-20 µm total tip diameter), attached to a four-channel pressure ejection system developed and built in the laboratory, were used to pressure-eject agents into the midbrain and brain stem. The volume of ejectate was measured by observing the level of the fluid meniscus through a graduated monocular microscope eyepiece (7 nl/division), and the amount of drug administered could be controlled by altering the ejected volume either by changing driving pressure, duration, or frequency of the driving pressure. An ejection marker was recorded on tape for later analysis.
The drugs for microinjection were diluted in a vehicle of artificial cerebrospinal fluid (aCSF) containing 1% Pontamine sky blue dye adjusted to pH 7.2-7.4 to mark ejection sites. Microinjections of vehicle (20 nl) were made as controls for volume and pressure effects of ejected solution. The agents used were the synaptic excitant, D,L-homocysteic acid (DLH; 0.1 M; Sigma-Aldrich) and the specific 5-HT1A receptor antagonist WAY-100635 [WAY; (N-[2-[-4-2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexane-carboxamide maleate; 1 mM; Research Biochemicals International].
A double-barreled micropipette was inserted at coordinates targeting the vlPAG, and vehicle was ejected (20 nl) as a control. In the absence of vehicle effects, 20 nl DLH was microinjected, and the effect on sympathetic nerve activity and arterial blood pressure was monitored. Adjustments of electrode position were made until a site was located at which DLH evoked a decrease in sympathetic nerve activity and blood pressure (control 1). After 30 min, the microinjection of DLH was repeated (control 2) to ensure reproducibility of the sympathoinhibitory and depressor responses. The remaining protocol was only performed at sites at which the control response could be repeated. The micropipette remained at the site in the vlPAG, and a second multibarreled micropipette was inserted at coordinates targeting the region of the RVLM. The RVLM micropipette was inserted ipsilateral to the side of vlPAG stimulation because the descending pathway from vlPAG to RVLM is considered to be primarily ipsilateral (7, 8). DLH (7 nl) was microinjected, with fine adjustment of coordinates as necessary, to locate a site at which a pressor response with an increase of at least 20 mmHg and an accompanying increase in sympathetic nerve activity was evoked. This protocol was used to indicate tip placement in the RVLM region containing sympathoexcitatory neurons. The 5-HT1A receptor antagonist, WAY (14 nl), was then ejected at the RVLM pressor site, and after 2 min the microinjection of DLH in the vlPAG was repeated while the effects on sympathetic nerve activity and blood pressure were monitored. The response to activation of vlPAG neurons by DLH microinjection was subsequently examined at 30-min intervals after the RVLM administration of WAY to determine recovery of the vlPAG-evoked response. In three control animals, the protocol was followed as outlined above, except that DLH was microinjected into the RVLM to locate sites adjacent to the sympathoexcitatory region from which no change in blood pressure or sympathetic nerve activity was evoked.
To confirm that WAY does not have a nonspecific effect on neurons in the sympathoexcitatory region of the RVLM, the viability of the baroreflex was tested in four animals before and after blockade of 5-HT1A receptors in the sympathoexcitatory region of the RVLM. The pressor region of the RVLM was identified by microinjection of DLH from a multibarreled glass micropipette, as described above. Baroreceptors were then activated by administration of phenylephrine (6 µg/kg iv) to raise arterial pressure by ~50 mmHg, and the reflex inhibition of renal sympathetic nerve activity was monitored. After a recovery period of 30 min, WAY (14 nl, 1 mM) was microinjected from a separate barrel of the micropipette located in the sympathoexcitatory region of the RVLM, baroreceptor activation was repeated 2 min later, and the sympathetic response was monitored.
We were unable to quantify the blood pressure response in one animal for the second control (control 2) and in one animal for the response after the microinjection of WAY.
Data analysis. Analysis of taped data of peripheral nerve recordings was performed by sampling blood pressure and averaged nerve activity at a rate of 20 Hz for a prestimulus period, stimulus period, and poststimulus period using a Hewlett-Packard 310 computer equipped with an Infotek 16-channel, 12-bit analog-to-digital converter. An analysis program was used to display blood pressure and averaged nerve activity on a computer monitor along with a movable cursor. The cursor was set at the onset of the stimulus and acted as a zero time marker for the analysis. Nerve activity and blood pressure were averaged over sequential 20-s periods, relative to the cursor, before, during, and after the stimulus, and subsequently expressed as percentage changes from two averaged 20-s prestimulus periods. To eliminate noise, zero nerve activity was obtained at the end of the experiment by crushing each nerve proximal to the recording electrodes, averaging the remaining noise levels, and subtracting them from the respective averaged activities. The percent change in activity from control levels was compared before and after antagonist administration for each protocol using one-way or multiple analysis of variance. Duncan's post hoc test was employed with the level of significance set at P < 0.05.
For identification of the location of central microinjection sites, brains were removed postmortem and frozen. Sequential 20-µm frozen, transverse sections of tissue through the medulla and midbrain were cut, stained with neutral red, and examined microscopically to identify and locate the microinjection sites histologically.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Activation of neurons in the vlPAG of the rat by microinjection of
the synaptic excitant DLH could elicit an inhibition of renal and
lumbar sympathetic nerve activities and a decrease in arterial blood
pressure (Figs. 1A and
2A). Sympathoinhibition was
evident in all rats, with peak inhibition occurring at 40-60 s
after the injection of DLH into the vlPAG. Renal nerve activity was
decreased significantly from control by 35.9 ± 5.1% (n = 9) at 60 s after microinjection of DLH into the vlPAG (Fig.
3A). Lumbar sympathetic nerve
activity was also decreased significantly from control by 31.8 ± 6.8% (n = 8) at 60 s after microinjection of DLH
into the vlPAG (Fig. 3B). At 60 s after DLH
microinjection, arterial blood pressure decreased significantly by
10.7 ± 1.8 mmHg (n = 15) below control levels of
135.1 ± 6.8 mmHg (n = 15; Fig. 3C).
Nerve activities and blood pressure began to return to baseline by 2 min after microinjection of DLH into the vlPAG. The inhibition evoked
in the lumbar sympathetic nerve was not significantly different to that
evoked in the renal sympathetic outflow (Figs. 2A and
4). Reproducibility of the vlPAG-evoked response (control 1) was examined by repeating the DLH
microinjection after 30 min (control 2). When compared, the
magnitude of the peak sympathoinhibition of 
34.4 ± 5.0% for
control 1 vs. 28.4 ± 3.0% for control 2 (n = 17) and the hypotension evoked for control 1 (10.2 ± 1.8 mmHg) vs. control 2 (9.0 ± 1.9 mmHg) (n = 14) were not significantly different.
The sites in the PAG from which microinjection of DLH could elicit
sympathoinhibition were located ventrolateral to the aqueduct at the
rostral level of the dorsal raphe nucleus (Fig.
5).
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Microinjections of DLH (7 nl) were made in the RVLM to identify sites
at which an increase in arterial blood pressure over 20 mmHg and an
accompanying increase in sympathetic nerve activity could be evoked
(Fig. 1B), indicative of activation of sympathoexcitatory neurons. Once recovery of baseline activities and blood pressure to
control values at these sites were obtained, WAY was microinjected from
another barrel of the micropipette. Microinjection of WAY into the RVLM
had no significant effect on baseline nerve activities (99.3% of
control; n = 17) or blood pressure (96.9% of control; n = 14). However, the sympathoinhibition evoked from
the vlPAG was significantly attenuated or eliminated after blockade of
5-HT1A receptors in the RVLM (Figs. 1, C and
D; 2B; and 3, A and B), with summed data showing an insignificant increase in renal and lumbar
sympathetic nerve activities from control levels. Similarly, arterial
blood pressure was increased slightly above control levels (Fig.
3C). In most cases, some recovery of the sympathoinhibitory response was evident 30 min after the microinjection of WAY. The antagonist effects of WAY were not generalized, as baroreflex inhibition of sympathetic nerve activity was not affected by
microinjection of WAY into the sympathoexcitatory region of the RVLM
(Fig. 6) in the four animals tested.
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The vlPAG-evoked sympathetic response after blockade of
5-HT1A receptors in the RVLM fell into two categories. In 7 of 15 animals, there was no change in renal and lumbar sympathetic
nerve activities in response to vlPAG stimulation after microinjection of WAY into the RVLM pressor area (Figs. 2 and
7A). In 8 of 15 animals, the
vlPAG-evoked sympathoinhibitory response was converted into a
sympathoexcitatory response, with a peak >5% of control level (Figs.
1C and 7B). With blockade of 5-HT1A
receptors in the RVLM, the sympathetic response to activation of vlPAG
neurons was 42.3 ± 14% (n = 9) above control
levels at 40 s after microinjection of DLH in to the vlPAG.
Microinjection sites of WAY in the pressor region of the RVLM were
verified histologically to be located in the lateral region of nucleus
paragigantocellularis lateralis at the rostral level of the inferior
olives (Fig. 5).
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In three control experiments, WAY was microinjected at sites adjacent
to the pressor region of the RVLM from which microinjection of DLH did
not produce an increase in lumbar sympathetic nerve activity or
hypertension. The effect on the sympathoinhibition evoked from the
vlPAG was examined before and after microinjection of WAY at these
sites. Microinjection of WAY at sites outside of the pressor region had
no significant effect on the sympathoinhibition evoked from the vlPAG
(Fig. 8). Lumbar sympathetic
nerve activity was reduced by 44 ± 6.4% (n = 3)
before microinjection of WAY outside of the RVLM pressor region vs.
35 ± 4.3% (n = 3) after microinjection of WAY.
In addition to this control, multiple microinjections of DLH were made
at the same site in the vlPAG at 30-min intervals for 3 h, each
made 2 min after microinjection of WAY outside of the pressor area of
the RVLM. The vlPAG-evoked sympathoinhibition was reproducible over
time, showing no attenuation of the inhibitory response over the 3-h
period.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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This study demonstrates that microinjection of the synaptic excitant DLH into the vlPAG can elicit a sympathoinhibitory response accompanied by hypotension that can be attenuated by blockade of 5-HT1A receptors in the RVLM. The target sites for microinjection of the 5-HT1A receptor antagonists in the RVLM were the sympathoexcitatory neurons, because previous studies have indicated that the site of action of 5-HT1A agonists in the mediation of a sympathoinhibitory and depressor response was at sympathoexcitatory neurons. The anatomic foundation has been provided by immunohistochemical studies that located 5-HT1A receptors on catecholaminergic and noncatecholaminergic spinally projecting RVLM neurons (16). Furthermore, microinjection of the 5-HT1A receptor agonist 8-OH-DPAT into localized regions of the RVLM can elicit differential patterns of sympathoinhibition in regional sympathetic outflows (1) potentially due to modulation of the activity of topographically dedicated RVLM sympathoexcitatory neurons (13). Electrophysiological evidence implicates the involvement of the 5-HT1A receptor subtype on RVLM sympathoexcitatory neurons in the mediation of a serotonergically mediated sympathoinhibition. The discharge rate of putative sympathoexcitatory neurons in the RVLM can be reduced by local application of 5-HT1A receptor agonists (20, 37), a response that can be blocked by prior ejection of WAY (unpublished observations). Furthermore, indication of the specificity of WAY (14) was provided by evidence that the baroreflex inhibition of renal sympathetic nerve activity, mediated by GABA receptors on sympathoexcitatory neurons in the RVLM (32) was not affected by blockade of 5-HT1A receptors in the sympathoexcitatory region of the RVLM. This demonstrates that WAY does not have a nonspecific effect on sympathoinhibitory responses mediated through RVLM sympathoexcitatory neurons. In the present study, microinjection sites in the region of sympathoexcitatory neurons of the RVLM were verified physiologically by the observation of a pressor response and increased sympathetic nerve activity induced by microinjection of DLH before microinjection of the 5-HT1A receptor antagonist WAY. When microinjected into an adjacent region of the RVLM from which a pressor response could not be evoked by microinjection of DLH, WAY was ineffective in attenuating the vlPAG-evoked sympathoinhibition. Taken together, these data support the contention that the sympathoinhibition elicited from vlPAG neurons is mediated through 5-HT1A receptors on sympathoexcitatory neurons of the RVLM. The finding that blockade of 5-HT1A receptors in the RVLM has no effect on resting, baseline levels of sympathetic nerve activity or blood pressure suggests that these receptors do not contribute to the tonic control of arterial blood pressure but rather are activated in a modulatory role in response to a specific challenge. Hypotension, induced by sympathoinhibition, is an integral component of a number of physiological responses thought to be coordinated in the PAG. Severe hemorrhage (18, 19), in which a centrally mediated hypotensive response follows the initial sympathoexcitation and tachycardia, analgesia (24), and the recovery phase of a defense reaction (39) are responses with which activation of RVLM 5-HT1A receptors may be associated to produce the hypotensive effect.
In the present study, there was no significant difference in the magnitude of the sympathoinhibition evoked in the renal vs. the lumbar sympathetic nerve by activation of neurons in the vlPAG. These data do not support the concept of differential control of regional sympathetic outflow by vlPAG neurons, for which there is evidence in the cat model (7, 8). However, brain size and technical limitations in the rat model may preclude the observation of differential control of sympathetic outflows, as has been indicated for activation of different RVLM neuron populations (4).
At ~50% of the sites examined, the vlPAG-evoked sympathoinhibition was converted to a sympathoexcitatory response after blockade of 5-HT1A receptors in the RVLM. This sympathoexcitatory response could be due to activation of unblocked 5-HT2 receptors located in the RVLM, their effect unmasked by selective blockade of the 5-HT1A receptor subtype. Activation of 5-HT2 receptors is generally considered to elicit excitatory effects at barosensitive neurons in the RVLM (38), and whereas 5-HT evokes primarily an inhibition of RVLM barosensitive neuronal discharges, a biphasic response has been noted (25). The magnitude of the sympathoexcitatory response after blockade of 5-HT1A receptors could depend on the location of the microinjection site with respect to 5-HT2 receptors. In addition, activation of vlPAG neurons primarily evokes an inhibition of the discharges of barosensitive RVLM neurons, but a biphasic response has been reported from microinjections at adjacent sites (38). Activation of neurons at a site of overlap of functionally heterogenous neurons could evoke a mixed sympathetic response. Attenuation of an inhibitory component by blockade of RVLM 5-HT1A receptors could allow the excitatory component to be revealed. The excitation may be mediated by other 5-HT receptor subtypes, by another neurotransmitter in the RVLM, or via an alternative pathway. In contrast, the sites from which the vlPAG-evoked sympathoinhibitory responses were abolished after blockade of 5-HT1A receptors in the RVLM may have been centered among functionally similar neurons.
The question remains whether the sympathoinhibitory pathway from vlPAG to RVLM is direct or indirect. Serotonin-containing cells have been localized in the vlPAG (31), and there is evidence to support a direct pathway from vlPAG to RVLM. Hypotension and differential increases in regional vascular conductance evoked from the vlPAG of the cat may be mediated by neurons arranged viscerotopically in the rostrocaudal direction projecting to topographically arranged RVLM neurons destined for specific regional sympathetic outflows (7). Nontransneuronal retrograde tracing from RVLM in both the cat (7) and the rat (35) suggests that this pathway may be direct. However, anterograde tracing from vlPAG indicated few fibers labeled in the sympathoexcitatory region of the RVLM (35). In contrast, there appears to be a dense innervation of raphe magnus (3), an area that projects to the RVLM (23, 28, 33, 34) and is rich in serotonin-containing neurons (12, 31). Electrophysiological evidence also supports the involvement of rostral raphe neurons in the inhibition of RVLM unit activity evoked from vlPAG (39). Additionally, other studies indicate projections from the vlPAG to the caudal medullary raphe (18), a region from which depressor responses can be mediated by inhibition of RVLM sympathoexcitatory neurons (36). Therefore, the sympathoinhibition evoked by activation of vlPAG neurons may be mediated at least in part via an indirect pathway from the vlPAG through the midline raphe to the RVLM, although the precise raphe nuclei involved remain undetermined. Although the serotonergic component of a sympathoinhibitory pathway from vlPAG to RVLM may project from the vlPAG or midline raphe, it is also possible that it is a local projection within the RVLM.
Perspectives
The function of a serotonergically mediated sympathoinhibition elicited from vlPAG neurons remains to be established but it may prove to be important under a variety of conditions. The PAG is a heterogenous midbrain structure, and the vlPAG is associated with a number of behavioral conditions that integrate hypotension and a decrease in heart rate with which the serotonergically mediated sympathoinhibition could be involved. Analgesia can be evoked from the vlPAG and can be accompanied by hypotension (24), which may be mediated, at least in part, through the RVLM. The decrease in blood pressure and heart rate evoked from the vlPAG has been compared with that observed after an initial sympathoexcitation during severe hemorrhage, and a role for the caudal midline medulla in the mediation of the sympathoinhibitory events has been suggested (18, 19). A depressor and sympathoinhibitory response evoked from the caudal midline raphe has been shown to be mediated by inhibition of RVLM sympathoexcitatory neurons (34), although the neurotransmitters involved remain to be determined. It has also been suggested that the inhibition of the activity of RVLM neurons elicited by vlPAG stimulation contributes to the recovery phase after a defense response (39). The vlPAG-RVLM sympathoinhibitory pathway may be a unique or a common component of these different responses. Further investigations are necessary to determine the pathway of the serotonergically mediated sympathoinhibition mediated through the RVLM and to determine its role as a component of complex behavioral events integrated in part in the vlPAG.| |
ACKNOWLEDGEMENTS |
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The authors thank C. A. Hermes and A. R. Cowan for excellent technical and histological assistance.
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FOOTNOTES |
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This work was supported by the National Science Foundation Grant IBN-9723348.
Address for reprint requests and other correspondence: C. Dean, Dept. Anesthesiology/151, Zablocki VA Medical Center, Milwaukee, WI 53295 (E-mail: cdean{at}mcw.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 1 August 2000; accepted in final form 7 November 2000.
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REFERENCES |
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TOP
ABSTRACT
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MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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, from response at 20 s;
and 
, from response before blockade of RVLM 5-HT1A
receptors, P < 0.05.
, n = 9) and LSN (
, n = 8) activities and
arterial BP (
, n = 15) in response to
activation of neurons in the vlPAG, illustrating no differential
control of regional sympathetic outflows.
,
RSN; 
, LSN; 
, RSN and LSN recorded simultaneously.
Shaded square, control microinjection sites outside of the pressor
region of the RVLM. DR, dorsal raphe nucleus; IO, inferior olivary
nuclei; NA nucleus ambiguus; R, midline raphe; VII, facial nucleus.
) microinjection of the
5-HT1A receptor antagonist WAY (1 mM, 14 nl) outside of the
pressor region of the RVLM (n = 3). The responses were
not significantly different.