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1 Department of Physiology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo 04023-060, Brazil; and 2 Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229-3900
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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N-methyl-D-aspartate
(NMDA) and non-NMDA excitatory amino acid (EAA) receptor subtypes are
involved in the integration of visceral afferent inputs within the
nucleus of the solitary tract (NTS). Microinjection studies indicate
interactions between nitric oxide (NO) and EAA receptors within the
NTS. To examine these interactions at the single cell level, this study
characterized the effects of the NO synthase inhibitor
NG-nitro-L-arginine methyl ester
(L-NAME) and the NO donor
3-[2-hydroxy-2-nitroso-1-propylhydrazino]-1-propanamine (PAPA-NONOate) on the excitatory responses of vagus nerve
(VN)-evoked NTS neurons to the activation of
(RS)-
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in rats. Iontophoresis of
L-NAME did not alter spontaneous or VN-evoked discharges,
but significantly decreased the number of action potentials (APs)
evoked by iontophoretic application of AMPA. The effects of
L-NAME on NMDA-evoked discharge were variable; for the
population, L-NAME did not change the number of APs evoked
by NMDA. PAPA-NONOate enhanced the spontaneous discharge and the number
of APs elicited by AMPA but not NMDA. Iontophoresis of the inactive
enantiomers NG-nitro-D-arginine
methyl ester and hydroxydiazenesulfonic acid 1-oxide disodium salt had
no effect on AMPA-evoked discharge. Our data suggest that NO
facilitates AMPA-mediated neuronal transmission within the NTS.
nucleus of the solitary tract; N-methyl-D-aspartate; (RS)--amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; vagus nerve stimulation
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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IN VIVO AND IN VITRO STUDIES report that the activation of glutamatergic receptors in the central nervous system increases the production and release of nitrosothiol substances (9, 29, 42). Nitric oxide (NO) is an unstable radical that undergoes either nitrosation chemistry or reaction with superoxide (14, 32, 39). The product of these reactions can affect modulatory sites on excitatory amino acid (EAA) receptors and alter neuronal responses to activation of these receptors (11, 17, 28, 32, 39, 40).
NO modulation of EAA responses can result in facilitation or
inhibition depending on the specific brain area affected. NO facilitates responses to EAAs within the hippocampus (12,
13), the lateral geniculate nucleus (5), and the
ventrobasal thalamus (37), to provide a few examples. In
other areas, such as the cerebellum (38) and the
periaqueductal grey (24), NO appears to mediate or
facilitate inhibition. In certain areas, NO modulation of EAA receptors
is even more complicated: in the dorsal horn of the spinal cord,
inhibition of NO synthase (NOS) attenuates N-methyl-D-aspartate (NMDA) responses and
facilitates
(RS)--amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
(AMPA) responses (2).
The first synapses within the central nervous system for the visceral afferent fibers of the vagus nerve (VN) occur in the nucleus of the solitary tract (NTS). Numerous studies have reported that these afferent terminals release L-glutamate and NO among other neurotransmitters (7, 10, 21). Vagal afferents to the NTS contain NOS (16, 21), and vagal deafferentation decreases NOS immunoreactivity in the NTS (25). Immunohistochemical approaches have demonstrated the colocalization of neuronal NOS (nNOS) and the NMDA receptor subunit NMDAR1 as well as the AMPA receptor subunit GLuR1 in single neurons in the NTS of rats (22). NOS immunoreactivity has also been found in neurons in many nuclei within the medulla oblongata that send projections to the NTS, which suggests that NO generated in the NTS may modulate vagal afferent integration (7). Therefore, sources of NO within the NTS are peripheral afferent inputs to the nucleus, local interneurons within the NTS, and inputs from other central sites to the NTS.
Physiological studies also suggest a role for NO within the NTS in the modulation of cardiovascular function. Microdialysis and microinjection studies have shown that NOS inhibitors reduce extracellular levels of glutamate (19) and the cardiovascular responses to NTS microinjection of ionotropic EAA agonists (20, 30). Activation of cardiopulmonary afferent inputs results in the release of NO, which activates soluble guanylate cyclase within the NTS (18). Microinjection of soluble guanylate cyclase inhibitors into the NTS reduces the cardiovascular responses to microinjection of ionotropic EAA agonists into the NTS (42). Single unit recording studies from NTS neurons indicate that NOS inhibitors decrease spontaneous discharge (26) and NO donors increase spontaneous discharge.
All of these results suggest that NO may modulate visceral afferent integration within the NTS by modulating neuronal responses to EAA receptor activation. The specific aim of this study was to use single unit recording and iontophoretic techniques to examine the modulation by NO of NMDA- and AMPA-evoked discharges in VN-evoked NTS neurons.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals. Experiments were performed on Sprague-Dawley rats (300-400 g body wt; Charles River). Rats were housed two per cage in a laboratory animal room and had unrestricted access to food and water. All animals were given at least 1 wk to acclimate to the environment before use. All experimental protocols were approved by the Institutional Animal Care and Use Committee.
Preparation. Animals were anesthetized with Inactin (100 mg/kg ip; Sigma) and placed on a thermostatically controlled heating pad. The trachea was cannulated and the rat was artificially ventilated with room air supplemented with 100% O2. The cervical VN including the aortic and laryngeal branches ipsilateral to the site of central recording was isolated and marked with a small loop of black suture. Catheters were placed in the femoral artery and vein for blood pressure monitoring and injection of drugs. Arterial pressure was measured using a Cobe CDX transducer (Cobe Laboratories; Lakewood, CO). Mean arterial pressure (in mmHg) and heart rate (in beats/min) were determined from the pulsatile signal using a Coulbourn blood pressure processor. Gallamine thiethiodide (20 mg/kg initially supplemented with 5 mg as needed, typically every hour) was also given for paralysis. Depth of anesthesia was gauged by the stability of blood pressure and heart rate and the absence of a pressor response to paw pinch. The rat was placed in a stereotaxic frame, and an occipital craniotomy was performed to expose the dorsal surface of the medulla in the region of obex. The previously isolated VN was placed on bipolar stimulating electrodes and covered with a mixture of mineral oil and Vaseline petroleum jelly.
Electrophysiological recordings. Extracellular action potential (AP) discharge was recorded with a five-barreled electrode. The recording barrel was filled with a solution of 0.5 M sodium acetate that contained 2% Chicago sky blue. One barrel of each five-barrel electrode was filled with a solution of 3 M NaCl and used for current balancing and pH controls. The other barrels were filled with different drug solutions (see Drugs and drug administration). Recordings were obtained from the region 1.2 mm caudal and 0.5 mm rostral to the calamus scriptorius, 0-0.8 mm lateral to the midline, and 0.2-1 mm below the surface. The electrode was lowered into the tissue in 2.0-µm steps by a step-driver controller (Burleigh Instruments; Fisher, NY). The VN was stimulated with single pulses of 1 ms in duration, 0.5 Hz, and 500 µA. If the neuron responded with an AP to each of two VN stimuli separated by 5 ms, the input was considered monosynaptic; otherwise, the input was considered polysynaptic.
APs were recorded and amplified by a direct current amplifier (World Precision Instruments; New Haven, CT) passed through an alternating current filter and sent to a digital oscilloscope (Nicolet Instruments; Madison, WI), an audiomonitor (Grass Instruments; Quincy, MA), a videotape recorder (A. R. Vetter; Rederburg, PA), and a window discriminator (World Precision Instruments; Sarasota, FL). The window-discriminator output was led to a Cambridge Electronic Design (model CED1401; Cambridge, UK) analog-to-digital converter interfaced with a personal computer. For on-line and off-line analyses, Spike 2 data-acquisition software was used.Drugs and drug administration. Drugs were administered by application of microiontophoretic ejecting currents to the drug-containing barrels. The drug solutions for microiontophoresis were 10 mM AMPA (Tocris Cookson; Bristol, UK), 100 mM NMDA (Sigma; St. Louis, MO), 50 mM NG-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor; Sigma), 50 mM NG-nitro-D-arginine methyl ester (D-NAME; Sigma), 50 mM 3-[2-hydroxy-2-nitroso-1-propylhydrazino]-1-propanamine (PAPA-NONOate or NOC-15, a NO donor; Sigma), and 50 mM hydroxydiazenesulfonic acid 1-oxide disodium salt (sulfo-NONOate, a negative control of PAPA-NOate; Sigma). Drugs were dissolved in 150 mM NaCl, and pH was adjusted to 8.0-8.5 for AMPA and NMDA, 6.5 for L-NAME and D-NAME, and 8.0 for PAPA-NONOate and sulfo-NONOate. All drugs were ejected as anions. Retaining currents of appropriate polarity were applied to the drug barrels to retain the passive diffusion of the drug from the electrode tip during nonejection periods.
NO modulation of EAA responses was studied as follows: after the baseline spontaneous discharge rate was recorded, VN-evoked neurons were excited by pulsatile iontophoretic application of 10-20 nA of NMDA or AMPA (control) until a steady-state level of evoked discharge was reached. NMDA and AMPA were ejected for successive 7- to 8-s periods separated by 10- to 15-s intervals (Fig. 1). At this point, the iontophoresis of the excitatory agents was stopped, and a continuous iontophoretic ejection of L-NAME, PAPA-NONOate, or the respective enantiomer was begun. After ~2 min, the pulsatile application of AMPA or NMDA was begun again. After the AMPA- or NMDA-evoked discharge reached a steady state, iontophoresis of the excitatory agent and either the L-NAME, PAPA-NONOate, or the respective enantiomer was stopped. After a 3- to 5-min recovery period, the pulsatile application of AMPA or NMDA was begun again to determine whether altered responses had returned to control levels. To examine NO modulation of synaptic inputs, poststimulus time histograms of 30 responses to 0.5-Hz VN stimulation were obtained before, during, and after iontophoresis of L-NAME.
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Data analysis. Neuronal responses to iontophoretic application of NMDA and AMPA were obtained by subtracting the number of APs during the drug ejection period from the number of APs measured during an equivalent-duration baseline period. The number of APs was counted during a 10-s period that began with the onset of the iontophoretic ejection pulse. AMPA- and NMDA-evoked discharges were averaged over three or four cycles once the level of discharge had reached the steady state. AMPA- and NMDA-evoked discharges are presented as absolute numbers of APs. Rate-meter records (no. of APs/s) were used for statistical analysis of the spontaneous discharge rate, and these data are presented as a frequency (in Hz). All data were analyzed by repeated-measures ANOVA and subsequent Student's modified t-test with Student-Newman-Keuls test. Significance was accepted at a 0.05 confidence level.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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General characteristics of neurons studied. Successful recordings were obtained from 42 VN-evoked neurons in 26 rats. The average onset latency for VN-evoked excitation was 2.5 ± 0.2 ms. In 8 neurons, the vagal afferent input exhibited characteristics consistent with a monosynaptic input (onset latency, 2.3 ± 0.5 ms), whereas in the remaining 34 neurons, the input appeared to be polysynaptic (onset latency, 2.6 ± 2.2 ms). There were no differences between these two groups in any of the parameters examined, and therefore they are grouped together in the subsequent analyses. Spontaneous discharge was present in 34 neurons and averaged 1.1 ± 0.2 Hz.
Responses for 17 of the 34 neurons were observed after injection of 16 µg of phenylbiguanide into the right atrium to discern a thoracic cardiopulmonary site of origin for the vagal afferent input. Of the 17 neurons, 10 were excited, 5 were inhibited, 1 did not respond, and 1 responded with an excitatory response followed by an inhibitory response.Effects of L-NAME on AMPA- and NMDA-evoked discharges in VN-evoked NTS neurons. Iontophoresis of L-NAME (20-80 nA, 2-5 min) did not alter spontaneous discharge rates (2.4 ± 0.5 vs. 2.5 ± 0.7 Hz; n = 15). Iontophoresis of L-NAME had no effect on discharge evoked by VN stimulation (no. of APs evoked by 30 stimuli at 0.5 Hz: control, 26 ± 3; during iontophoresis of L-NAME, 27 ± 3; n = 11).
The number of APs evoked by pulsatile AMPA iontophoresis was reduced during coiontophoresis of L-NAME (Fig. 1). For the population, AMPA-evoked discharge was decreased from 44 ± 7 to 29 ± 6 APs (P = 0.002; n = 14; Fig. 2). As a control for possible nonspecific effects of L-NAME, the inactive enantiomer D-NAME was applied in a manner similar to that described for L-NAME. Iontophoresis of D-NAME (40 nA) did not alter spontaneous discharge (control, 3.0 ± 0.5; D-NAME, 2.8 ± 0.5 Hz; n = 5). In addition, D-NAME did not alter the number of APs evoked by AMPA (control, 64 ± 12; D-NAME, 69 ± 9; n = 5).
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Effects of PAPA-NONOate on AMPA- and NMDA-evoked discharges of
VN-evoked NTS neurons.
In 12 VN-evoked neurons, AMPA-evoked discharge was examined during
iontophoresis of the NO donor PAPA-NONOate using the same protocol as
in the L-NAME studies. Two cells had no spontaneous discharge before and during iontophoresis of PAPA-NONOate, and one cell
had an inordinately high spontaneous discharge rate of 8.8 Hz and was
excluded from analysis. The NO donor increased the spontaneous
discharge of six of the remaining nine cells from a control level of
1.8 ± 3 to 3.2 ± 7 Hz during iontophoresis of PAPA-NONOate
(P = 0.03; n = 9; Fig.
5A).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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This study shows that AMPA receptor-mediated excitation of NTS neurons that receive vagal afferent inputs can be facilitated by NO. Inhibition of NOS by L-NAME significantly decreased the number of APs evoked by AMPA receptor stimulation. The NO donor PAPA-NONOate significantly enhanced the rate of spontaneous discharge and the number of APs evoked by AMPA. The inhibition of NOS by L-NAME did not significantly decrease the number of APs evoked by NMDA receptor stimulation when measured for the population as a whole. In the majority of NTS neurons, NMDA-evoked discharge was not altered by inhibition of NOS. However, there was a small number of neurons in which NMDA-evoked discharge was either facilitated or attenuated during iontophoresis of L-NAME. Reciprocal effects of NO on AMPA- vs. NMDA-evoked discharge have been reported for the spinal cord dorsal horn (2).
In the present study, iontophoresis of L-NAME decreased the number of APs evoked by AMPA receptor stimulation in all neurons tested, but the number of APs evoked by NMDA receptor activation was decreased in 40% of the cells. This result was surprising, because the relationship between NO and NMDA receptors has been studied in other systems, where it has been shown that NMDA receptor activation results in an entrance of Ca2+ into the cell that activates NOS and reduces subsequent NMDA-evoked responses (11, 17, 27). Such an inhibitory feedback mechanism operating during prolonged activation of NMDA receptors could be a protective mechanism against glutamate-induced neurotoxicity (39). It is possible that the timing of administration or the concentration of NO donors and NOS inhibitors during iontophoretic application might explain why we observed variable changes in NMDA-evoked discharge during the L-NAME treatment. Sensitivity to NO may vary in different populations of cells (39). Therefore, interactions between NMDA receptors and NO in the NTS might be related to the specific reflex function(s) of a given cell.
The role of ionotropic glutamate receptors (NMDA and non-NMDA) in the integration of visceral afferent inputs within the NTS has been well demonstrated (1, 3, 8, 15, 33, 35, 36, 44). Many observations also suggest a role for NO within the NTS in cardiovascular regulation. Intravenous administration of L-NAME reduced the vasodilation in the hindquarter bed caused by glutamate microinjection into the NTS (4), which suggests modulation of glutamatergic excitation by nitroxidergic mechanisms within the NTS. Other in vivo studies showed that microinjection of L-arginine reduced heart rate, renal sympathetic nerve activity (RSNA), and blood pressure, whereas microinjection of a NOS inhibitor increased RSNA and blood pressure (43). These effects may be dependent on ionotropic glutamate receptors, because the microinjection of NMDA and non-NMDA receptor antagonists decreased the effects of L-arginine (20).
Visceral afferent inputs to the NTS can generate NO, and this NO may modulate afferent integration in the dorsal vagal complex and autonomic reflex function (18, 34). Vagal afferents and terminals that contain nNOS are present in the NTS, and deafferentation of VN fibers causes a reduction in NOS staining in the NTS (16, 23, 34, 42). The differential distribution of nNOS in the NTS supports the idea of NO modulation of autonomic reflexes (22). The presence of NOS immunoreactivity colocalized with NMDA receptor subunit NMDAR1 and AMPA receptor subunit GluR1 in the NTS of the rat suggests a modulatory role of NOS activity on EAA receptor activation (43). The subunits NMDAR1 and GluR1 are mainly localized on postsynaptic structures, and our study observed the postsynaptic discharge evoked by stimulation of these receptors on NTS neurons.
Our studies cannot definitively determine whether NO modulates EAA-evoked responses at presynaptic and/or postsynaptic sites. Our results suggest that this modulation can occur at a postsynaptic site, because our protocol examined effects of direct application of EAA agonists independently of synaptic inputs. However, NO-stimulated release of glutamate might contribute to the enhanced spontaneous discharge rate observed during iontophoresis of the NO donor in our study. The administration of NO via microdialysis induced glutamate release, whereas NOS inhibition reduced the basal level of glutamate in the NTS (19). A recent study demonstrated a facilitatory effect of NO on the release of glutamate when NMDA receptors were stimulated in the NTS, which enhanced the hypotension and bradycardia that is normally observed during activation of NMDA receptors in NTS (30). Therefore, although our data suggest a postsynaptic site for NO-EAA interactions, it does not preclude presynaptic interactions.
The lack of inhibition of VN-evoked discharge during iontophoresis of L-NAME was surprising to us, as we predicted that NO would modulate synaptic inputs. However, the lack of inhibition is likely the result of our protocol. We examined VN-evoked discharge using a low stimulus frequency, 0.5 Hz. We speculate on the basis of data obtained from the cell illustrated in Fig. 4 that NO may be of functional importance during periods of high-frequency discharge, and our VN stimulus paradigm did not evoke high-frequency discharge. Similarly, we failed to observe a reduction in spontaneous discharge rate during iontophoresis of the NOS inhibitor, whereas two previous studies of NTS neurons have shown such a reduction (26, 41). This difference could be explained by the relative discharge frequencies of the NTS neurons. In the present study, spontaneous discharge was low (1-3 Hz), whereas in the study of Ma et al. (26), spontaneous discharge frequency was 5-6 Hz. Absolute frequencies were not reported in the study of Tagawa et al. (41). The increase in spontaneous discharge that was observed during iontophoresis of the NO donor could be the result of modulation of synaptic inputs; however, it could also be the result of changes in postsynaptic excitability.
The decrease in the number of APs evoked by AMPA during NOS inhibition suggests that NO facilitates AMPA transmission within the NTS. Consistent with this, we observed a significant increase in the number of APs evoked by AMPA microiontophoresis in the presence of the NO donor PAPA-NONOate. This compound is considered to be a pure NO donor in that it releases only NO (40) and does not release other substances that could interfere with the neuron or affect NOS activity. Our data reinforce the hypothesis that AMPA receptor-evoked excitation can be facilitated by NO. The lack of effect on low-frequency VN-evoked discharges and the dose-response relationship obtained from one neuron suggest that this facilitation may only come into play when the neuron is driven into a high-discharge-frequency state. This would provide a means of sustaining excitatory transmission rate during periods when transmitter depletion or other factors might otherwise reduce excitation.
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ACKNOWLEDGEMENTS |
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The authors gratefully acknowledge the support of National Heart, Lung, and Blood Institute Grants HL-41894 and HL-56637 (to S. W. Mifflin). A. C. R. Dias was partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Award BEX 0761/00-1.
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FOOTNOTES |
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Address for reprint requests and other correspondence: S. W. Mifflin, Dept. of Pharmacology, MC 7764, Univ. of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900 (E-mail: mifflin{at}uthscsa.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.
10.1152/ajpheart.00037.2002
Received 17 January 2002; accepted in final form 22 August 2002.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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|---|
1.
Aylwin, ML,
Horowitz JM,
and
Bonham AC.
NMDA receptors contribute to primary visceral afferent transmission in the nucleus of solitary tract.
J Neurophysiol
77:
2539-2548,
1997
2.
Budai, D,
Wilcox GL,
and
Larson AL.
Effects of nitric oxide availability on responses of spinal wide dynamic range neurons to excitatory amino acids.
Eur J Pharmacol
278:
39-47,
1995[ISI][Medline].
3.
Chan, RKW,
and
Sawchenko PE.
Organization and transmitter specificity of medullary neurons activated by sustained hypertension: implications for understanding baroreceptor reflex circuitry.
J Neurosci
18:
371-387,
1998
4.
Colombari, E,
Davisson RL,
Shaffer RA,
Talman WT,
and
Lewis SJ.
Hemodynamic effects of L-glutamate in NTS of conscious rats: a possible role of vascular nitrosyl factors.
Am J Physiol Heart Circ Physiol
274:
H1066-H1074,
1998
5.
Cudeiro, J,
Rivadulla C,
Rodriguez R,
Martinez-Conde S,
Martinez L,
Grieve KL,
and
Acuña C.
Further observations on the role of nitric oxide in the feline lateral geniculate nucleus.
Eur J Neurosci
8:
144-152,
1996[ISI][Medline].
6.
Drewe, JA,
Miles R,
and
Kunze DL.
Excitatory amino acid receptors of guinea pig medial nucleus tractus solitarius neurons.
Am J Physiol Heart Circ Physiol
259:
H1389-H1395,
1990
7.
Esteves, FOG,
McWilliam PN,
and
Batten TFC
Nitric oxide producing neurones in the rat medulla oblongata that project to nucleus solitarii.
J Chem Neuroanat
20:
185-197,
2000[ISI][Medline].
8.
Foley, CM,
Moffitt JA,
Hay M,
and
Hasser EM.
Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors.
Am J Physiol Regul Integr Comp Physiol
275:
R1858-R1866,
1998
9.
Garthwaite, J,
Garthwaite G,
Palmer RM,
and
Moncada S.
NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices.
Eur J Pharmacol
172:
413-416,
1989[ISI][Medline].
10.
Gordon, FJ,
and
Talman WT.
Role of excitatory amino acids and their receptors in bulbospinal control of cardiovascular function.
In: Central Neural Mechanisms in Cardiovascular Regulation. New York: Birkhauser, 1992, p. 209-225.
11.
Hoyt, KR,
Tang LH,
Aizenman E,
and
Reynolds IJ.
Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons.
Brain Res
592:
310-316,
1992[ISI][Medline].
12.
Izumi, Y,
Clifford DB,
and
Zorumski CF.
Inhibition of long-term potentiation by NMDA-mediated nitric oxide release.
Science
257:
1273-1276,
1992
13.
Kato, K,
and
Zorumski CF.
Nitric oxide inhibitors facilitate the induction of long-term potentiation by modulating NMDA responses.
J Neurophysiol
70:
1260-1263,
1993
14.
Krukoff, TL.
Central regulation of autonomic function: NO brakes? Satellite symposium on neural mechanisms in hypertension.
Clin Exp Pharmacol Physiol
25:
474-478,
1998[ISI][Medline].
15.
Kubo, T,
and
Kihara M.
Unilateral blockade of excitatory amino acid receptors in the nucleus tractus solitarii produces an inhibition of baroreflexes in rats.
Naunyn Schmiedebergs Arch Pharmacol
343:
317-322,
1991[ISI][Medline].
16.
Lawrence, AJ,
Castillo-Melendez M,
McLean KJ,
and
Jarrott B.
The distribution of nitric oxide synthase-, adenosine deaminase- and neuropeptide Y-immunoreactivity through the entire rat nucleus tractus solitarius: effect of unilateral nodose ganglionectomy.
J Chem Neuroanat
15:
27-40,
1998[ISI][Medline].
17.
Lei, SZ,
Pan ZH,
Aggarwal SK,
Chen HSV,
Hartman J,
Sucher NJ,
and
Lipton SA.
Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex.
Neuron
8:
1087-1099,
1992[ISI][Medline].
18.
Lewis, SJ,
Machado BH,
Ohta H,
Bates JN,
and
Talman WT.
Microinjection of S-nitrosocysteine into the nucleus tractus solitarii decreases arterial pressure and heart rate via activation of soluble guanylate cyclase.
Eur J Pharmacol
202:
135-136,
1991[ISI][Medline].
19.
Lin, HC,
Kang BH,
Wan FJ,
Huang ST,
and
Tseng CJ.
Reciprocal regulation of nitric oxide and glutamate in the nucleus tractus solitarii of rats.
Eur J Pharmacol
407:
83-89,
2000[ISI][Medline].
20.
Lin, HC,
Wan FJ,
and
Tseng CJ.
Modulation of cardiovascular effects produced by nitric oxide and ionotropic glutamate receptor interaction in the nucleus tractus solitarii of rats.
Neuropharmacology
38:
935-941,
1999[ISI][Medline].
21.
Lin, LH,
Cassel MD,
Sandra A,
and
Talman WT.
Direct evidence for nitric oxide synthase in vagal afferents to the nucleus tractus solitarii.
Neuroscience
84:
549-558,
1998[ISI][Medline].
22.
Lin, LH,
Sahai AK,
Rockland KS,
and
Talman WT.
The distribution of neuronal nitric oxide synthase in nucleus tractus solitarii of the aquirrel monkey.
Brain Res
856:
84-92,
2000[ISI][Medline].
23.
Lin, LH,
Sandra A,
Boutelle S,
and
Talman WT.
Up-regulation of nitric oxide synthase and its mRNA in vagal motor nuclei following axotomy in rat.
Neurosci Lett
221:
97-100,
1997[ISI][Medline].
24.
Lovick, TA,
and
Key BJ.
Inhibitory effect of nitric oxide on neuronal activity in the periaqueductal grey matter of the rat.
Exp Brain Res
108:
382-388,
1996[ISI][Medline].
25.
Lü, Y,
Ding YQ,
Quin BZ,
and
Li JS.
The distribution and origin of axon terminals with NADPH diaphorase activity in the nucleus of the solitary tract of the rat.
Neurosci Lett
171:
70-72,
1994[ISI][Medline].
26.
Ma, S,
Abboud FM,
and
Felder RB.
Effects of L-arginine-derived nitric oxide synthesis on neuronal activity in nucleus tractus solitarius.
Am J Physiol Regul Integr Comp Physiol
268:
R487-R491,
1995
27.
Manzoni, O,
Prezeau L,
Marin P,
Deshager S,
Bockaert J,
and
Fagni L.
Nitric oxide-induced blockade of NMDA receptors.
Neuron
8:
653-662,
1992[ISI][Medline].
28.
Manzoni, O,
Prezeau L,
Marin P,
Deshager S,
Bockaert J,
and
Fagni L.
Sodium nitroprusside blocks NMDA receptors via formation of ferrocyanide ions.
Neuroreport
3:
77-80,
1992[ISI][Medline].
29.
Marin, P,
Quignard JF,
Lafon-Cazal M,
and
Bockaert J.
Non-classical glutamate receptors, blocked by both NMDA and non-NMDA antagonists, stimulate nitric oxide production in neurons.
Neuropharmacology
32:
29-36,
1993[ISI][Medline].
30.
Matsuo, I,
Hirooka Y,
Hironaga K,
Eshima K,
Shigematsu H,
Shihara M,
Sakai K,
and
Takeshita A.
Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo.
Am J Physiol Regul Integr Comp Physiol
280:
R1285-R1291,
2001
31.
Miller, BD,
and
Felder RB.
Excitatory amino acid receptors intrinsic to synaptic transmission in nucleus tractus solitarii.
Brain Res
456:
333-343,
1988[ISI][Medline].
32.
Moncada, S,
Palmer RM,
and
Higgs EA.
Nitric oxide: physiology, pathophysiology, and pharmacology.
Pharmacol Rev
43:
109-142,
1991[ISI][Medline].
33.
Ohta, H,
and
Talman WT.
Both NMDA and non-NMDA receptors in the NTS participate in the baroreceptor reflex in rats.
Am J Physiol Regul Integr Comp Physiol
267:
R1065-R1070,
1994
34.
Ruggiero, DA,
Mtui EP,
Otake K,
and
Anwar M.
Central and primary visceral afferents to nucleus tractus solitarii may generate nitric oxide as a membrane-permeant neuronal messenger.
J Comp Neurol
364:
51-67,
1996[ISI][Medline].
35.
Seagard, JL,
Dean C,
and
Hopp FA.
Neurochemical transmission of baroreceptor input in the nucleus tractus solitarius.
Brain Res Bull
51:
111-118,
2000[ISI][Medline].
36.
Seagard, JL,
Dean C,
and
Hopp FA.
Role of glutamate receptors in transmission of vagal cardiac input to neurones in the nucleus tractus solitarii in dogs.
J Physiol (Lond)
520:
243-253,
1999
37.
Shaw, PJ,
and
Salt TE.
Modulation of sensory and excitatory amino acid responses by nitric oxide donors and glutathione in the ventrobasal thalamus of the rat.
Eur J Neurosci
9:
1507-1513,
1997[ISI][Medline].
38.
Shibuki, K,
and
Okada D.
Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum.
Nature
349:
326-328,
1991[Medline].
39.
Shuman, EM,
and
Madison DV.
Nitric oxide and synaptic function.
Annu Rev Neurosci
17:
153-183,
1994[ISI][Medline].
40.
Stamler, JS,
Toone EJ,
Lipton SA,
and
Sucher NJ.
(S) NO signals: translocation, regulation, and a consensus motif.
Neuron
18:
691-696,
1997[ISI][Medline].
41.
Tagawa, T,
Imaizumi T,
Harada S,
Endo T,
Shiramoto M,
Hirooka Y,
and
Takeshita A.
Nitric oxide influences neuronal activity in the nucleus tractus solitarius of rat brainstem slices.
Circ Res
75:
70-76,
1994
42.
Talman, WT,
Dragon DN,
Otha H,
and
Lin LH.
Nitroxidergic influences on cardiovascular control by NTS: a link with glutamate.
Ann NY Acad Sci
940:
169-78,
2001
43.
Tseng, CJ,
Liu HY,
Lin Hui-C,
Ger LP,
Tung CS,
and
Yen MH.
Cardiovascular effects of nitric oxide in the brain stem nuclei of rats.
Hypertension
27:
36-42,
1996
44.
Zhang, J,
and
Mifflin SW.
Differential roles for NMDA and non-NMDA receptor subtypes in baroreceptor afferent integration in the nucleus of the solitary tract of the rat.
J Physiol
511:
733-745,
1998
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)
represents an individual neuron (n = 16). Normal range
of variability in such evoked responses, ±10%, is indicated (dashed
lines).
