Role of glutamate in a visceral sympathoexcitatory reflex in rostral ventrolateral medulla of cats

2006 ◽  
Vol 291 (3) ◽  
pp. H1309-H1318 ◽  
Author(s):  
Wei Zhou ◽  
Liang-Wu Fu ◽  
Stephanie C. Tjen-A-Looi ◽  
Zhi-ling Guo ◽  
John C. Longhurst
Keyword(s):  
Receptor Antagonist ◽  
Ampa Receptors ◽  
Glutamate Transporter ◽  
Rostral Ventrolateral Medulla ◽  
Visceral Afferents ◽  
Ventrolateral Medulla ◽  
Double Labeling ◽  
Excitatory Neurotransmitter ◽  
Reflex Responses ◽  
Arterial Blood

The rostral ventrolateral medulla (rVLM) is involved in processing visceral sympathetic reflexes. However, there is little information on specific neurotransmitters in this brain stem region involved in this reflex. The present study investigated the importance of glutamate and glutamatergic receptors in the rVLM during gallbladder stimulation with bradykinin (BK), because glutamate is thought to function as an excitatory neurotransmitter in this region. Stimulation of visceral afferents activated glutamatergic neurons in the rVLM, as noted by double-labeling with c-Fos and the cellular vesicular glutamate transporter 3 (VGLUT3). Visceral reflex activation significantly increased arterial blood pressure as well as extracellular glutamate concentrations in the rVLM as determined by microdialysis. Barodenervation did not alter the release of glutamate in the rVLM evoked by visceral reflex stimulation. Iontophoresis of glutamate into the rVLM enhanced the activity of sympathetic premotor cardiovascular rVLM neurons. Also, the responses of these neurons to visceral afferent stimulation with BK were attenuated significantly (70%) by blockade of glutamatergic receptors with kynurenic acid. Microinjection of either an N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanate (25 mM, 30 nl) or an dl-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (2 mM, 30 nl) into the rVLM significantly attenuated the visceral sympathoexcitatory reflex responses. These results suggest that glutamate in the rVLM serves as an excitatory neurotransmitter through a baroreflex-independent mechanism and that both NMDA and AMPA receptors mediate the visceral sympathoexcitatory reflex responses.

Cardiovascular effects of opioid antagonist naloxone in rostral ventrolateral medulla of rabbits

1990 ◽  
Vol 258 (2) ◽  
pp. R325-R331 ◽  
Author(s):  
D. A. Morilak ◽  
G. Drolet ◽  
J. Chalmers
Keyword(s):  
Pressor Response ◽  
Cardiovascular Effects ◽  
Rostral Ventrolateral Medulla ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Ventrolateral Medulla ◽  
Inhibitory Influence ◽  
Beneficial Effects ◽  
Arterial Blood ◽  
Depressor Effect

We have examined the influence of endogenous opioids on the basal and reflex control of arterial blood pressure in the pressor region of the rostral ventrolateral medulla (RVLM) of chloralose-anesthetized rabbits. We tested basal effects both in intact animals and after hypotensive hemorrhage. Bilateral administration of the opiod antagonist naloxone (20 nmol, 100 nl) directly into the RVLM induced a gradual and prolonged increase in mean arterial pressure (MAP) (+17 +/- 2 mmHg). This was preceded by a brief and mild depressor effect (-9 +/- 3 mmHg), which was attributable to a transient reduction in excitability immediately after naloxone injection. When naloxone was administered into the RVLM after hemorrhage (20 ml/kg), it improved recovery of MAP relative to saline controls, again producing a gradual, prolonged pressor response (+29 +/- 5 mmHg). The effect of naloxone on a baroreflex in intact animals was only transient, with a brief, nonsignificant attenuation of the reflex depressor response to aortic nerve stimulation. We conclude that endogenous opioids exert a tonic inhibitory influence on RVLM pressor neurons and that this input remains active after hemorrhage. The RVLM may thus be one site for the beneficial effects of naloxone in preventing circulatory decompensation after hemorrhage. In contrast, opioid neurons are not an essential component of baroreflex-mediated sympathoinhibition in the RVLM.

scholarly journals Synaptic and extrasynaptic transmission of kidney-related neurons in the rostral ventrolateral medulla

2013 ◽  
Vol 110 (11) ◽  
pp. 2637-2647 ◽  
Author(s):  
Hong Gao ◽  
Andrei V. Derbenev
Keyword(s):  
Large Scale ◽  
Critical Role ◽  
Input Resistance ◽  
Rostral Ventrolateral Medulla ◽  
Kainate Receptors ◽  
Ventrolateral Medulla ◽  
Resting Membrane Potential ◽  
Arterial Blood ◽  
Whole Cell Patch Clamp ◽  
Tonic Current

The rostral ventrolateral medulla (RVLM) is a critical component of the sympathetic nervous system regulating homeostatic functions including arterial blood pressure. Using the transsynaptic retrograde viral tracer PRV-152, we identified kidney-related neurons in the RVLM. We found that PRV-152-labeled RVLM neurons displayed an unusually large persistent, tonic current to both glutamate, via N-methyl-d-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/kainate receptors, and to γ-aminobutyric acid (GABA), via GABAAreceptors, in the absence of large-scale phasic neurotransmission with whole cell patch-clamp recordings. A cocktail of potent NMDA and AMPA/kainate ionotropic glutamate receptor antagonists AP-5 (50 μM) and CNQX (10 μM) revealed a two-component somatic tonic excitatory current with an overall amplitude of 42.6 ± 13.4 pA. Moreover, application of the GABAAreceptor blockers gabazine (15 μM) and bicuculline (30 μM) revealed a robust somatic tonic inhibitory current with an average amplitude of 196.3 ± 39.3 pA. These findings suggest that the tonic current plays a role in determining the resting membrane potential, input resistance, and firing rate of RVLM neurons. The magnitude of the tonic inhibitory current demonstrates that GABAergic inhibition plays a critical role in regulation of kidney-related RVLM neurons. Our results indicate that the GABAergic tonic current may determine the basal tone of firing activity in kidney-related RVLM neurons.

5-Hydroxytryptamine Responses in Immature Rat Rostral Ventrolateral Medulla Neurons In Vitro

1998 ◽  
Vol 80 (3) ◽  
pp. 1033-1041 ◽  
Author(s):  
L. L. Hwang ◽  
N. J. Dun
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Reversal Potential ◽  
Input Resistance ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Immature Rat ◽  
Apparent Change ◽  
Biphasic Responses

Hwang, L. L. and N. J. Dun. 5-Hydroxytryptamine responses in immature rat rostral ventrolateral medulla neurons in vitro. J. Neurophysiol. 80: 1033–1041, 1998. Whole cell patch recordings were made from rostral ventrolateral medulla (RVLM) neurons of brainstem slices from 8- to 12-day-old rats. By superfusion or pressure ejection to RVLM neurons, 5-hydroxytryptamine (5-HT) elicited three types of membrane potential changes: a slow hyperpolarization (5-HTH), a slow depolarization (5-HTD) and a biphasic response, which persisted in a tetrodotoxin (TTX, 0.3 μM)-containing solution. 5-HTH were accompanied by a decrease of input resistance in the majority of responsive neurons. Hyperpolarization reduced and depolarization increased the 5-HTH; the mean reversal potential was −92.3 mV in 3.1 mM and shifted to −69.3 mV in 7 mM [K+]o. Barium (Ba2+, 0.1 mM) but not tetraethylammonium (TEA, 10 mM) suppressed 5-HTH. The 5-HT1A receptor agonist (±)-8-hydroxy-dipropylamino-tetralin (8-OH-DPAT; 5–50 μM) hyperpolarized RVLM neurons. The 5-HT1A antagonist pindobind-5-HT1A (PBD; 1–3 μM) and the 5-HT2/5-HT1 receptor antagonist spiperone (1–10 μM) suppressed 5-HTH and the hyperpolarizing phase of biphasic responses; the 5-HT2 receptor antagonist ketanserin (3 μM) was without significant effect. 5-HTD were associated with an increase or no apparent change of input resistance in RVLM neurons. Hyperpolarization of the membrane decreased or caused no apparent change in 5-HTD. 5-HTD were reduced in an elevated [K+]o (7.0 mM) solution and >60% in a low Na+ (26 mM) solution and were not significantly changed in a low Cl− (6.7 mM) or Ca2+-free/high Mg2+ (10.9 mM) solution. The 5-HT2 receptor agonist α-methyl-5-HT (50 μM) depolarized RVLM neurons, and the 5-HT2 antagonist ketanserin (1–10 μM) attenuated the 5-HTD and the depolarizing phase of biphasic responses, whereas the 5-HT1A receptor antagonist PBD (2 μM) was without effect. Inclusion of the hydrolysis resistant guanine nucleotide GDP-β-S in patch solution significantly reduced the 5-HTH as well as the 5-HTD. The present study shows that, in the immature rat RVLM neurons, 5-HT causes a slow hyperpolarization and depolarization probably by interacting with 5-HT1A and 5-HT2 receptors, which are G-proteins coupled. 5-HTH may involve an increase of an inwardly rectifying K+ conductance, and 5-HTD appear to be caused by a decrease of K+ conductance and/or increase of nonselective cation conductance.

scholarly journals Spinal nociceptin mediates electroacupuncture-related modulation of visceral sympathoexcitatory reflex responses in rats

2009 ◽  
Vol 297 (2) ◽  
pp. H859-H865 ◽  
Author(s):  
Wei Zhou ◽  
Aman Mahajan ◽  
John C. Longhurst
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Intrathecal Injection ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Reflex Modulation ◽  
Reflex Responses ◽  
Pressor Responses ◽  
Pressor Reflex

The role of nociceptin and its spinal cord neural pathways in electroacupuncture (EA)-related inhibition of visceral excitatory reflexes is not clear. Nociceptin/orphanin FQ (N/OFQ) is an endogenous ligand for a G protein-coupled receptor, called the N/OFQ peptide (NOP) receptor, which has been found to be distributed in the spinal cord. The present study investigated the importance of this system in visceral-cardiovascular reflex modulation during EA. Cardiovascular pressor reflex responses were induced by gastric distension in Sprague-Dawley rats anesthetized by ketamine and xylazine. An intrathecal injection of nociceptin (10 nM) at T1–2 attenuated the pressor responses by 35%, similar to the influence of EA at P 5–6 (42% decrease). An intrathecal injection of the NOP antagonist, [ N-Phe1]nociceptin1-13 NH2, partially reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not alter the EA-like inhibitory effect of nociceptin on the pressor reflex, whereas a combination of nociceptin receptor antagonist with naloxone completely abolished the EA response. An intrathecal injection of nociceptin attenuated the pressor responses to the electrical stimulation of the rostral ventrolateral medulla by 46%, suggesting that nociceptin can regulate sympathetic outflow. Furthermore, a bilateral microinjection of NOP antagonist into either the dorsal horn or the intermediolateral column at T1 partially reversed the EA inhibitory effect. These results suggest that nociceptin in the spinal cord mediates part of the EA-related modulation of visceral reflex responses.

scholarly journals Enhancement in Tonically Active Glutamatergic Inputs to the Rostral Ventrolateral Medulla Contributes to Neuropathic Pain-Induced High Blood Pressure

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Wang ◽  
Zui Zou ◽  
Xing Tan ◽  
Ru-Wen Zhang ◽  
Chang-Zhen Ren ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Neuropathic Pain ◽  
Cardiovascular Diseases ◽  
High Blood Pressure ◽  
Glutamate Transporter ◽  
Rostral Ventrolateral Medulla ◽  
Infraorbital Nerve ◽  
Ventrolateral Medulla ◽  
Sympathetic Overactivity ◽  
High Level

Neuropathic pain increases the risk of cardiovascular diseases including hypertension with the characteristic of sympathetic overactivity. The enhanced tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM) contributes to sympathetic overactivity and blood pressure (BP) in cardiovascular diseases. We hypothesize that neuropathic pain enhances tonically active glutamatergic inputs to the RVLM, which contributes to high level of BP and sympathetic outflow. Animal model with the trigeminal neuropathic pain was induced by the infraorbital nerve-chronic constriction injury (ION-CCI). A significant increase in BP and renal sympathetic nerve activity (RSNA) was found in rats with ION-CCI (BP, n=5, RSNA, n=7, p<0.05). The concentration of glutamate in the RVLM was significantly increased in the ION-CCI group (n=4, p<0.05). Blockade of glutamate receptors by injection of kynurenic acid into the RVLM significantly decreased BP and RSNA in the ION-CCI group (n=5, p<0.05). In two major sources (the paraventricular nucleus and periaqueductal gray) for glutamatergic inputs to the RVLM, the ION-CCI group (n=5, p<0.05) showed an increase in glutamate content and expression of glutaminase 2, vesicular glutamate transporter 2 proteins, and c-fos. Our results suggest that enhancement in tonically active glutamatergic inputs to the RVLM contributes to neuropathic pain-induced high blood pressure.

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