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1 Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michican 48824; and 2 Department of Pharmacology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This study was designed to test the hypothesis that 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) and clonidine reduce sympathetic nerve discharge (SND) and mean arterial pressure (MAP), in part by actions in the medullary lateral tegmental field (LTF). We microinjected these drugs bilaterally into the LTF of baroreceptor-innervated and -denervated cats anesthetized with Dial-urethane. Neither drug altered SND (as quantified by using power spectral analysis) or MAP when injected into the LTF of baroreceptor-denervated cats. However, cardiac-related power in SND was significantly increased to 148 ± 12 (mean ± SE) and 149 ± 5% of control by microinjections of 8-OHDPAT (n = 5) and clonidine (n = 5), respectively, in baroreceptor-innervated cats whose MAP was kept constant; there was no change in 0- to 6-Hz power or total power. SND was significantly reduced by microinjection of these drugs into the rostral ventrolateral medulla of baroreceptor-innervated and -denervated cats. In conclusion, although 8-OHDPAT and clonidine did not reduce SND when injected into the LTF, they acted in this region to facilitate baroreceptor reflex control of SND, as evidenced by a selective increase in cardiac-related power.
baroreceptor reflex; cardiac-related rhythm; entrainment; rostral ventrolateral medulla; sympathetic nerve discharge
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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NEURONS IN THE ROSTRAL VENTROLATERAL medulla (RVLM) project directly to the intermediolateral autonomic nucleus (IML) in the thoracolumbar spinal cord; chemical lesion or inactivation of this region virtually eliminates sympathetic nerve discharge (SND) and reduces blood pressure to levels seen after cervical spinal cord transection [see reviews by Barman and Gebber (6), Dampney (17), and Guyenet (23)]. Thus the RVLM is critical for the maintenance of basal SND and the normotensive state. These functions of the RVLM have been attributed to their intrinsic pacemaker properties (35, 36) and to synaptic drive from other brain stem regions (2, 5, 7, 28). Regarding the latter, Lipski et al. (28) recorded intracellularly from RVLM-spinal sympathoexcitatory neurons in anesthetized rats and found that their spontaneously occurring action potentials were preceded by fast excitatory postsynaptic potentials. Moreover, we (7) recently showed that microinjection of either an N-methyl-D-aspartate (NMDA) or non-NMDA excitatory amino acid receptor antagonist into the RVLM of baroreceptor-denervated cats significantly reduced SND (as quantified by using power density spectral analysis) and mean arterial pressure (MAP). This implies that synaptic input to RVLM neurons is involved in generating basal SND in cats.
As reviewed by Barman and Gebber (6), one source of synaptic input to RVLM-spinal sympathoexcitatory neurons in cats is the medullary lateral tegmental field (LTF), including portions of nucleus reticularis parvocellularis and nucleus reticularis ventralis in the dorsolateral medullary reticular formation. This region contains a mixture of tonically active sympathoexcitatory and sympathoinhibitory neurons (2, 3, 21), and the axons of LTF sympathoexcitatory neurons project to the RVLM (2). We (7) recently demonstrated that non-NMDA-mediated neurotransmission in the LTF plays a critical role in setting the basal level of SND in cats. Specifically, SND and MAP were significantly reduced by microinjection of a selective non-NMDA excitatory amino acid receptor antagonist into the LTF (7). In contrast, the cardiac-related rhythm in SND and the sympathoinhibitory response to activation of the baroreceptor reflex were reversibly eliminated by microinjection of a selective NMDA receptor antagonist into the LTF (32). Thus the LTF is also involved in mediating baroreceptor reflex control of SND.
From the data demonstrating an important role of LTF neurons in the
control of SND, the following question can be asked: Is the LTF a site
of action of drugs that work centrally to decrease SND and MAP? The
major aim of the current study was to test the hypothesis that the
5-hydroxytryptamine (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) and the
2-adrenoceptor agonist clonidine reduce SND in part by
an action in the LTF. This possibility was considered because the LTF
of the cat receives both serotonergic and catecholaminergic inputs
(19, 24). Because 8-OHDPAT and clonidine can reduce SND
and MAP by acting in the RVLM (10, 15, 25, 27, 29-31, 34,
37), in the current study, we compared the effects produced by
bilateral microinjection of these drugs into the LTF and RVLM of
baroreceptor-innervated and baroreceptor-denervated cats.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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General Procedures
The protocols used in these studies on 20 adult cats (2.0-4.3 kg) were approved by the All-University Committee on Animal Use and Care of Michigan State University. Cats were anesthetized with an intraperitoneal injection of a mixture of sodium diallylbarbiturate (60 mg/kg), urethane (240 mg/kg), and monoethylurea (240 mg/kg). Cats were paralyzed (4 mg/kg iv initial dose of gallamine triethiodide), pneumothoracotomized, and artificially respirated with room air. End-tidal CO2 was held near 4% (model 2200 capnometer, Traverse Medical Monitors), and rectal temperature was kept near 38°C with a heat lamp. Before neuromuscular blockade, the adequacy of anesthesia was indicated by the absence of a palpebral reflex. When cats were paralyzed, an adequate level of anesthesia was indicated by the inability of noxious stimuli (pinch, heat, surgery) to increase blood pressure and desynchronize the electroencephalogram (4).Baroreceptor-Innervated Cats
In 10 cats with intact baroreceptor nerves, MAP was maintained at the same level throughout the analysis period (i.e., before and after microinjection of 8-OHDPAT or clonidine into the medulla) to avoid changes in cardiac-related power in SND, which might have occurred as the result of a change in the level of baroreceptor nerve activity. An intravenous infusion of a mixture of norepinephrine bitartrate (1-3 µg/min) and dextran (6% in saline) was used to set MAP at a level (~120 mmHg) adequate to produce a prominent cardiac-related rhythm in SND (32, 38). The rate of infusion was adjusted during the experiment to keep MAP constant.Baroreceptor-Denervated Cats
The carotid sinus, aortic depressor, and vagus nerves were sectioned bilaterally in the other 10 cats. Two observations verified the completeness of baroreceptor denervation. First, spectral analysis failed to show a cardiac-related rhythm in SND (see Fig. 6). In barbiturate-anesthetized, baroreceptor-denervated cats, bursts of SND occur primarily at frequencies of
6 Hz, and there is no sign of a
10-Hz rhythm (26). Second, SND was not reflexly inhibited
during the pressor response produced by norepinephrine bitartrate
(1-2 µg/kg iv).
Neural Recordings
The methods used to make monophasic recordings of left inferior cardiac postganglionic SND can be found in earlier reports (2, 3, 21). The preamplifier band pass was 1-1,000 Hz. The synchronized discharges of populations of sympathetic nerve fibers appear as slow waves (i.e., envelopes of spikes) when this band pass is used (21).Microinjections
A 10 mM solution of 8-OHDPAT or a 30 mM solution of clonidine was microinjected bilaterally into the medulla (sites defined below) through a glass micropipette (~40-µm tip diameter) superglued to the needle of a 5-µl Hamilton syringe. Drugs were diluted in 0.9% saline; the solution was adjusted to a pH of 6-8 (litmus paper test). The syringe and micropipette were mounted on a microinjection unit (model 5000, David Kopf Instruments). A 100-nl injection of 8-OHDPAT (1 nmol) or clonidine (3 nmol) was made slowly (~20 s) at each medullary site by turning the calibrated micrometer on the microinjection unit.The dorsal surface of the brain stem was exposed by removing portions of the occipital bone and cerebellum. The midline and obex were used as landmarks for placement of the micropipette. The micropipette was positioned into the LTF in tracks located 2 and 3 mm rostral to the obex and 2.8 to 3 mm lateral to the midline. Microinjections were made bilaterally at depths of 3 and 4.5 mm from the dorsal surface. This region contains both putative sympathoexcitatory and sympathoinhibitory neurons (2, 3, 21). The micropipette was positioned into the RVLM in tracks located 4.5 and 5.5 mm rostral to the obex and 3.5 mm lateral to the midline. Microinjections were made bilaterally at depths of 4 and 5 mm from the dorsal surface. This region contains sympathoexcitatory neurons whose axons project directly to the IML (2, 5). Saline microinjections (100 nl, pH 6-8) into these medullary sites did not change SND in either baroreceptor-innervated or -denervated cats (7, 32, 34). The target sites for microinjection of 8-OHDPAT and clonidine into the LTF and RVLM were the same as that in studies in which we characterized the effects of microinjection of EAA receptor antagonists on basal SND and baroreceptor control of SND (see Fig. 1 in Refs. 7 and 32).
The protocol used in these studies was as follows. An 80-s control data block was collected after the micropipette was positioned at the first site to be injected. A complete set of injections into either the LTF or RVLM was then made on the left and right sides of the medulla. Test data blocks of 80 s were collected within 1-2 min after the last injection, again 5-10 min later, and then at 15-30 min intervals for up to 1 h to allow for partial or full recovery. The data block collected 5-10 min after the microinjection was used to quantify the effects of 8-OHDPAT or clonidine on SND. By this time, the maximum changes in SND had occurred, and SND had reached a steady-state level. Changes in MAP were also quantified at this time in baroreceptor-denervated cats.
Some cats were used for two sets of microinjections, one in the LTF and one in the RVLM. If microinjection of a drug into the LTF produced a change in SND, we waited for SND to return to near control level before injecting the same drug into the RVLM. If SND was unaffected by the first set of injections, we waited 30 min before microinjecting the same drug into the RVLM.
Data Analysis
SND was low-pass filtered at 100 Hz before all analyses were made on a Dell Optiplex GX110 computer; the Butterworth analog filter (model 260-5, A.P. Circuit) has unity gain and a roll-off rate of 24 dB/octave. Data were acquired (5-ms sampling intervals) with software and an analog-to-digital converter board from RC Electronics (Santa Barbara, CA). Frequency-domain analysis used a modified version (22) of the software of Cohen et al. (16) and Kocsis et al. (26).Fast Fourier transform was performed on 32 5-s windows of data with
50% overlap (80-s data block) to construct autospectra of left
inferior cardiac SND and the arterial pulse (AP) and a coherence
function relating SND to the AP. Spectral analyses were done over a
frequency band of 0-100 Hz with a resolution of 0.2 Hz/bin. The
figures in this report show only frequencies of 20 Hz because at
least 90% of the total power in SND was within this band
(26). The autospectrum of a signal shows how much power (voltage squared) is present at each frequency. The coherence function
(normalized cross-spectrum) is a measure of the strength of linear
correlation of two signals at each frequency. The squared coherence
value (referred to as coherence value) is one in the case of a perfect
linear relationship and zero, if two signals are unrelated. A coherence
value 
0.1 reflects a statistically significant relationship when 32 windows are averaged (8).
ASCII files of the data were saved for transfer to spreadsheet, graphics, and statistical programs (Statmost for Windows version 3.0, DataMost). The autospectra of SND before and after microinjection of 8-OHDPAT or clonidine were displayed on the same power scale. In baroreceptor-innervated cats, the cardiac-related band of SND was defined as the range of frequencies in the sharp peak in the autospectrum of SND centered at the frequency of the heartbeat. A macro written in Microsoft Excel version 7.0 was used to measure cardiac-related power. Briefly, a line was fitted to connect the left and right limits of the cardiac-related band of SND (see Fig. 2A, top); cardiac-related power was calculated as the area above this line. The 0- to 6-Hz power (including cardiac-related SND) was calculated by arithmetically summing the values for the bins in this frequency range. Total power was defined as the sum of the values for the bins between 0 and 20 Hz. In baroreceptor-denervated cats, 0- to 6-Hz power and total power were quantified.
Statistical Analysis
Data are expressed as means ± SE. The Student's paired t-test was used to compare MAP, power in specific frequency bands of SND, and AP-SND coherence values at the frequency of the heartbeat before and after microinjection of drugs into the brain stem. Coherence values were subjected to z-transformation before this analysis. Raw values of power were used for statistical analyses, but changes in SND are expressed as percentage of control in the text. P 0.05 indicated statistical significance.
Drugs
The following drugs were used: 8-OHDPAT hydrobromide, clonidine hydrochloride, and gallamine triethiodide (Sigma; St. Louis, MO) and norepinephrine bitartrate (Abbott; Chicago, IL). All drugs were dissolved in 0.9% saline. The doses of 8-OHDPAT and clonidine used in the current study were similar to those used in other microinjection studies (25, 30, 33, 34).Histology
The brain stem was removed and fixed in 10% buffered formalin. Frontal sections of 30-µm thickness were cut and stained with cresyl violet. Sites of microinjection were identified with reference to the bottom of the tracks made with the micropipette and the stereotaxic planes of Berman (9).| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Effects of Medullary Microinjections of 8-OHDPAT or Clonidine in Baroreceptor-Innervated Cats
8-OHDPAT.
We microinjected 8-OHDPAT bilaterally into the LTF of five
baroreceptor-innervated cats. Figures 1 and 2 show the results from one
of these cats. The bottom two histological sections in Fig.
1 show the tracks made by the
micropipette in the LTF at 2 and 3 mm rostral to the obex on the left
side of the medulla. As seen in the oscillographic record in Fig.
1A, bursts of SND were locked in a 1:1 relation to the AP
under control conditions. This was confirmed with spectral analysis;
i.e., the autospectra of SND and AP (Fig.
2A, top and
middle) have a sharp peak at the frequency of the heartbeat,
and the AP-SND coherence value at this frequency was 0.86 (Fig.
2A, bottom). Within 8 min after microinjecting
8-OHDPAT bilaterally into the LTF, the amplitude of the cardiac-related
bursts of SND was increased (Fig. 1B), and cardiac-related
power was 179% of control (Fig. 2B, top). In
contrast, 0- to 6-Hz and total power were essentially unchanged (109 and 102% of control, respectively). The AP-SND coherence value (0.90)
at the frequency of the heartbeat remained near control level (Fig.
2B, bottom). As described in METHODS,
MAP was held constant to prevent changes in cardiac-related power due
to altered levels of baroreceptor nerve activity (38).
Cardiac-related power returned to near control level within 30 min
(Fig. 2C, top).
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Clonidine.
We microinjected clonidine bilaterally into the LTF of five
baroreceptor-innervated cats. In the example shown in Fig.
5, cardiac-related power was increased to
167% of control (Fig. 5, A and B,
top) 5 min after microinjection of clonidine, and the AP-SND
coherence value at the frequency of the heartbeat was increased from
0.83 to 0.93 (Fig. 5, A and B,
bottom); 0- to 6-Hz power and total power were essentially
unchanged (103 and 108% of control, respectively). Cardiac-related
power returned to near control level within 25 min after microinjection
of clonidine (Fig. 5C). MAP was kept at 145 mmHg throughout
the experiment.
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Effects of Medullary Microinjections of 8-OHDPAT or Clonidine in Baroreceptor-Denervated Cats
8-OHDPAT.
We microinjected 8-OHDPAT bilaterally into the LTF of five
baroreceptor-denervated cats. In the representative example shown in
Fig. 6, the autospectrum of SND contained
a dispersed band of power, primarily at frequencies 6 Hz (Fig.
6A, top). Coherence analysis (Fig. 6A,
bottom) showed that there was no correlation between SND and
the AP (coherence value is not significantly different than zero),
indicating that baroreceptor denervation was complete (20,
32). As shown in Fig. 6B, top, the
autospectrum of SND was essentially unchanged after microinjection of
8-OHDPAT into the LTF. MAP was also basically unaffected (120 and 115 mmHg before and after injection, respectively). Subsequent
microinjection of 8-OHDPAT into the RVLM reduced 0- to 6-Hz and total
power in SND to 17 and 30% of control, respectively (Fig.
6C, top), and MAP was reduced to 65 mmHg. SND was
not changed by raising MAP back to control level with an intravenous
infusion of norepinephrine.
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Clonidine.
We microinjected clonidine bilaterally into the LTF of five
baroreceptor-denervated cats in which most of the power in SND was
distributed at frequencies 6 Hz. In the example shown in Fig.
8, 0- to 6-Hz power and total power in
SND were unchanged (102 and 100% of control, respectively) after
microinjection of clonidine (Fig. 8, top and
middle); MAP (130 mmHg) was also unaltered. When clonidine
was subsequently microinjected bilaterally into the RVLM of this cat
(Fig. 8, bottom), 0- to 6-Hz and total power were decreased
to 53 and 56% of control, respectively, and MAP was reduced to 115 mmHg.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The current study was designed to test the hypothesis that
8-OHDPAT and clonidine reduce SND, in part by actions in the LTF. Contrary to our expectations, SND and MAP were not significantly changed by microinjection of these drugs into the LTF of
baroreceptor-denervated cats. However, data from
baroreceptor-innervated cats revealed for the first time that these
drugs act in the LTF to facilitate baroreceptor reflex control of SND.
Specifically, microinjection of either 8-OHDPAT or clonidine into the
LTF increased cardiac-related power in SND under conditions in
which MAP was kept constant to prevent changes in SND due to
alterations in baroreceptor nerve activity (32). The
increase in cardiac-related SND occurred without a significant change
in 0- to 6-Hz power (sum of cardiac-related power plus background
power). This implies that cardiac-related SND increased because more of
the background power at frequencies 6 Hz became entrained to the
cardiac cycle due to facilitation of baroreceptor reflex control of SND
(20, 32).
The enhancement of cardiac-related SND produced by microinjection of
8-OHDPAT or clonidine into the LTF corroborates our earlier work
showing that the LTF is an important synaptic relay in the baroreceptor
reflex pathway controlling SND of the cat (32). The
effects of microinjection of 8-OHDPAT and clonidine were the reverse of
those produced by blockade of NMDA receptors in the LTF; microinjection
of an NMDA receptor antagonist reduced cardiac-related SND without
affecting 0- to 6-Hz power (32). Although we did not
determine the receptor types in the LTF involved in mediating the
effects of 8-OHDPAT and clonidine, these drugs are classified as
5-HT1A receptor and 2-adrenoceptor agonists,
respectively (1, 18, 30), and the LTF of the cat receives
both serotonergic and catecholaminergic inputs (19, 24).
Assuming that 8-OHDPAT and clonidine acted on monoaminergic receptors
in the LTF, the combined results from the current and earlier studies
suggest that activation of both NMDA and monoaminergic receptors in the LTF facilitates baroreceptor reflex control of SND.
Another index of the strength of baroreceptor-induced entrainment of SND is the coherence value relating SND to the AP at the frequency of the heartbeat. Although in individual cases (e.g., Fig. 5) this value was increased after microinjection of 8-OHDPAT or clonidine, the changes were not significant on a group basis. This was not surprising because the AP-SND coherence values were quite high in our experiments (control values close to 0.9). Thus we propose that the increase in cardiac-related SND primarily reflected recruitment of more central neurons into the pool entrained by pulse-synchronous baroreceptor nerve activity rather than improved cardiac locking of the discharges of neurons that were already entrained under control conditions.
At least two major issues need to be resolved regarding the actions of 8-OHDPAT and clonidine in the LTF of baroreceptor-innervated cats. First, are the receptors in the LTF that mediate the effects of these drugs innervated by monoaminergic inputs? If so, are these inputs tonically active in baroreceptor-innervated cats, or are they called into action reflexly or by forebrain inputs in the behaving animal? This issue can be addressed in future studies on the effects of local injections of monoaminergic antagonists into the LTF. Second, what specific mechanisms account for the selective increase in cardiac-related SND produced by microinjection of 8-OHDPAT or clonidine into the LTF? The LTF contains neurons that appear to be in the afferent limb of the baroreceptor reflex arc; i.e., neurons whose discharges remain locked to the AP during changes in heart rate that alter the phase relations between SND and the AP (20). If 8-OHDPAT and clonidine act to increase the excitability of these neurons, perhaps more LTF sympathoexcitatory neurons would be recruited into the pool that is entrained to the cardiac cycle by baroreceptor nerve activity. Alternatively, 8-OHDPAT and clonidine might have enhanced the sensitivity of LTF sympathoexcitatory neurons selectively to their pulse-synchronous baroreceptor reflex inputs. Either of these scenarios could explain why these drugs enhanced cardiac-related SND of baroreceptor-innervated cats without changing SND in baroreceptor-denervated cats.
The RVLM is viewed as a major site of action of 8-OHDPAT and clonidine to reduce SND and MAP when administered intravenously (10, 25, 27, 29-31, 34, 37). Indeed, there is a remarkable correlation between the decrease in the firing rate of RVLM-spinal sympathoexcitatory neurons and the inhibition of SND in response to intravenous administration of 8-OHDPAT or clonidine (1, 12, 15, 30, 37). In the current study, we confirmed that microinjection of either drug into the RVLM of baroreceptor-innervated or -denervated cats significantly reduces SND.
In contrast with the data presented in this report, the results of several studies implicate the LTF in mediating the sympathoinhibitory effects of 8-OHDPAT. Clement and McCall (13, 14) and Vayssettes-Courchay et al. (37) reported that LTF sympathoexcitatory neurons are inhibited in parallel to SND by intravenous administration of 8-OHDPAT, and kainic acid-induced lesions of the LTF prevent the decrease in SND produced by intravenous 8-OHDPAT. Whereas both sets of data support the view that the LTF was in the pathway that mediated the sympathoinhibitory effects of the drug, they do not prove that 8-OHDPAT acted directly in the LTF. The intravenously administered drug could have acted on a group of neurons antecedent to the LTF, thereby disfacilitating LTF sympathoexcitatory neurons. In this regard, data from our laboratory (7) support the view that synaptic drive to LTF sympathoexcitatory neurons accounts for a significant component of basal SND. It should also be pointed out that neuronal damage produced by kainic acid injections can extend beyond the site of injection; secondary effects of kainic acid injections include propagation of the excitotoxic injury in space and time by excessive neuronal firing (11).
Vayssettes-Courchay et al. (37) reported that microinjection of 8-OHDPAT into the LTF reduced SND by 23 ± 9%. This change was modest in comparison with the 51 ± 7% decrease in SND produced by microinjection of the same dose of 8-OHDPAT into the RVLM. The dose of 8-OHDPAT used by Vayssettes-Courchay et al. (37) was twice that used in the current study. Also, they showed that a considerably lower dose of the drug was effective when placed into the RVLM but not into the LTF. Thus they did not adequately rule out the possibility that the reduction in SND seen after microinjection of 8-OHDPAT into the LTF resulted from spread of the injectate to other medullary regions.
Clement and McCall (13) reported that LTF sym-pathoexcitatory neurons are inhibited by iontophoretic application of 8-OHDPAT. This raises the possibility that the lack of a decrease in SND with microinjection of 8-OHDPAT into the LTF in our experiments was due to inadequate doses or insufficient spread of the drug. This seems unlikely for two reasons. First, microinjection of the same dose of 8-OHDPAT into the RVLM markedly reduced SND and MAP. Second, the sites and volumes of injection in the LTF were the same as in experiments in which microinjections of non-NMDA and NMDA receptor antagonists significantly reduced SND and eliminated baroreflex control of SND, respectively (7, 32). Whereas it is possible that the diffusion of 8-OHDPAT differs from that of the excitatory amino acid receptor antagonists, the fact that 8-OHDPAT was injected into four LTF sites on each side of the medulla can be used to argue that the drug reached an adequate pool of LTF neurons involved in control of SND. Indeed, in baroreceptor-innervated cats, cardiac-related power in SND was significantly increased by microinjection of the same doses of 8-OHDPAT into the same LTF sites.
To our knowledge, this is the first study to assess the effects on SND of microinjection of clonidine into the LTF. Our conclusion that the LTF is not the site of action of clonidine to reduce SND and MAP is in agreement with the findings of Clement and McCall (14) and Vayssettes-Courchay et al. (37). They reported that the inhibition of SND produced by intravenous administration of clonidine was preserved after kainic acid-induced lesions of the LTF. Thus the major site of action of intravenous clonidine to reduce SND and MAP appears to be downstream from the LTF, likely in the RVLM (10, 31, 34, 37).
In summary, the LTF does not appear to play a role in mediating the
decreases in SND and MAP produced by intravenous administration of
8-OHDPAT and clonidine; however, these drugs can act in this region to
enhance the entrainment of centrally generated low frequency (6 Hz)
oscillations of SND to the cardiac cycle by pulse-synchronous baroreceptor nerve activity.
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ACKNOWLEDGEMENTS |
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This study was supported by National Heart, Lung, and Blood Institute Grant HL-33266.
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FOOTNOTES |
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Address for reprint requests and other correspondence: S. M. Barman, Dept. of Pharmacology and Toxicology, Michigan State Univ., East Lansing, MI 48824-1317 (E-mail: barman{at}msu.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 24 January 2001; accepted in final form 23 March 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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