scholarly journals Glutamate receptors in the hypothalamic paraventricular nucleus contribute to insulin-induced sympathoexcitation

2015 ◽  
Vol 113 (5) ◽  
pp. 1302-1309 ◽  
Author(s):  
Sean D. Stocker ◽  
Kathryn W. Gordon
Keyword(s):  
Paraventricular Nucleus ◽  
Excitatory Amino Acid ◽  
Isotonic Saline ◽  
Nmda Antagonist ◽  
Receptor Activation ◽  
Hypothalamic Paraventricular Nucleus ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Drug Treatments ◽  
Change In Mean

The sympathoexcitatory response to insulin is mediated by neurons in the arcuate nucleus (ARC) and hypothalamic paraventricular nucleus (PVH). Previous studies have reported that stimulation of ARC neurons increases sympathetic nerve activity (SNA) and arterial blood pressure (ABP) through glutamate receptor activation in the PVH. Therefore, the purpose of the present study was to determine whether glutamatergic neurotransmission in the PVH contributes to insulin-induced sympathoexcitation. Male Sprague-Dawley rats (275–400 g) were infused with isotonic saline or insulin (3.75 mU·kg−1·min−1) plus 50% dextrose to maintain euglycemia. Intravenous infusion of insulin significantly increased lumbar SNA without a significant change in mean ABP, renal SNA, heart rate, or blood glucose. Bilateral PVH injection of the excitatory amino acid antagonist kynurenic acid (KYN) lowered lumbar SNA and ABP of animals infused with insulin. Similarly, a cocktail of the NMDA antagonist dl-2-amino-5-phosphonopentanoic acid (AP5) and non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced lumbar SNA and mean ABP during infusion of insulin. In a final experiment, bilateral PVH injection of AP5 only, but not CNQX, lowered lumbar SNA and mean ABP of animals infused with insulin. The peak changes in lumbar SNA and mean ABP of insulin-treated animals were not different between KYN, AP5 plus CNQX, or AP5 alone. These drug treatments did not alter any variable in animals infused with saline. Altogether, these findings suggest that glutamatergic NMDA neurotransmission in the PVH contributes to insulin-induced sympathoexcitation.

scholarly journals Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4329-4335 ◽  
Author(s):  
Edith Sánchez ◽  
Praful S. Singru ◽  
Runa Acharya ◽  
Monica Bodria ◽  
Csaba Fekete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Early Action ◽  
Sprague Dawley Rats ◽  
Melanocortin Signaling ◽  
Agouti Related Protein ◽  
Serum Tsh

To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.

Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus

1991 ◽  
Vol 65 (4) ◽  
pp. 946-951 ◽  
Author(s):  
J. P. Wuarin ◽  
F. E. Dudek
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Guinea Pig ◽  
Paraventricular Nucleus ◽  
Excitatory Amino Acid ◽  
Hypothalamic Paraventricular Nucleus ◽  
Peak Amplitude ◽  
Kainate Receptor ◽  
Dose Dependent ◽  
Synaptic Responses

1. The effects of specific excitatory amino acid (EAA) antagonists on evoked excitatory synaptic responses were studied in the hypothalamic paraventricular nucleus (PVN) of the guinea pig, by the use of the in vitro slice preparation. Intracellular recordings were obtained from paraventricular neurons, and excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were induced by perifornical electrical stimulation. To reduce the influence of a potential gamma-aminobutyric acidA (GABAA) inhibitory component on the synaptic responses, all experiments were performed in the presence of 50 microM picrotoxin. 2. Of 20 cells tested, 13 had electrophysiological characteristics similar to magnocellular neuropeptidergic cells (MNCs) and 7 displayed low-threshold Ca2+ spikes (LTSs). No difference was detected in the effect of the antagonists on the synaptic responses of cells with or without LTS potentials. 3. The broad-spectrum EAA antagonist kynurenic acid decreased the amplitude of the EPSPs and EPSCs in a dose-dependent manner: the mean decrease was 5% for 100 microM, 43% for 300 microM, and 70% for 1 mM. 4. The quisqualate/kainate-receptor-selective antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) induced a dose-dependent decrease of the EPSPs and EPSCs: 1 microM had no detectable effect, 3 and 10 microM caused 30 and 70% decreases, respectively, and 30 microM blocked the response almost completely. This effect was not accompanied by a change in resting membrane potential or input resistance and was slowly reversible. 5. The N-methyl-D-aspartate (NMDA)-receptor-selective antagonist DL-2-amino-5-phosphonopentanoic acid (AP5), applied at 30 and 300 microM, reduced slightly the amplitude of the decay phase of the EPSP but did not significantly affect the peak amplitude. In some cells, the current-voltage relationship of the decay phase of the EPSC revealed a region of negative slope conductance between -70 and -40 mV. 6. These results suggest that 1) glutamate or a related EAA is responsible for the fast excitatory input to magnocellular and parvocellular neurons in the PVN and probably also for cells around PVN, 2) a quisqualate/kainate receptor type is responsible for the rising phase and peak amplitude of the synaptic current, and 3) an NMDA receptor contributes to the late part of the synaptic response.

Effect of NPY in the hypothalamic paraventricular nucleus on uncoupling proteins 1, 2, and 3 in the rat

2000 ◽  
Vol 278 (2) ◽  
pp. R494-R498 ◽  
Author(s):  
C. M. Kotz ◽  
C. F. Wang ◽  
J. E. Briggs ◽  
A. S. Levine ◽  
C. J. Billington
Keyword(s):  
Adipose Tissue ◽  
Paraventricular Nucleus ◽  
Uncoupling Protein ◽  
Biceps Femoris ◽  
Hypothalamic Paraventricular Nucleus ◽  
Sprague Dawley ◽  
Biceps Femoris Muscle ◽  
Sprague Dawley Rats ◽  
Brown Adipose ◽  
Specific Regulation

Neuropeptide Y (NPY) injected into the hypothalamic paraventricular nucleus (PVN) stimulates feeding and decreases uncoupling protein (UCP)-1 mRNA in brown adipose tissue (BAT). The present studies were undertaken to determine whether UCP-2 in white adipose tissue (WAT) and UCP-3 in muscle are regulated by NPY in the PVN. PVN-cannulated male Sprague-Dawley rats were injected with either saline or NPY (PVN, 117 pmol, 0.5 μl) every 6 h for 24 h. NPY in the PVN stimulated feeding and decreased UCP-1 mRNA in BAT independent of NPY-induced feeding. UCP-2 mRNA in WAT was unchanged by NPY. In acromiotrapezius muscle, NPY decreased UCP-3 mRNA, but this was reversed by restricting food intake to control levels. In biceps femoris muscle, NPY alone had no effect on UCP-3 mRNA, but UCP-3 mRNA was significantly increased in the NPY-treated rats that were restricted to control levels of intake. These results suggest that UCP-2 in WAT and UCP-3 in muscle are not subject to specific regulation by NPY in the PVN.

scholarly journals Stimulation of the hypothalamic paraventricular nucleus modulates cardiorespiratory responses via oxytocinergic innervation of neurons in pre-Bötzinger complex

2007 ◽  
Vol 102 (1) ◽  
pp. 189-199 ◽  
Author(s):  
S. O. Mack ◽  
M. Wu ◽  
P. Kc ◽  
M. A. Haxhiu
Keyword(s):  
Heart Rate ◽  
Paraventricular Nucleus ◽  
Pseudorabies Virus ◽  
Upper Airway ◽  
Hypothalamic Paraventricular Nucleus ◽  
Electromyographic Activity ◽  
Arterial Blood ◽  
Bötzinger Complex ◽  
Receptor Signaling Pathway ◽  
Induced Changes

Previously we reported that oxytocin (OT)-containing neurons of the hypothalamic paraventricular nucleus (PVN) project to the pre-Bötzinger complex (pre-BötC) region and phrenic motoneurons innervating the diaphragm (D). The aim of these studies was to determine pathways involved in PVN stimulation-induced changes in upper airway and chest wall pumping muscle activity. In addition, we determined the role of OT-containing neurons in the PVN in mediating increased respiratory output elicited by PVN stimulation. Neuroanatomical experiments, using pseudorabies virus (PRV) as a transneuronal tracer in C8 spinalectomized animals showed that PVN neurons project to hypoglossal motoneurons innervating the genioglossus (GG) muscle. Furthermore, microinjection of the PVN with bicuculline, a GABAA receptor antagonist, significantly increased ( P < 0.05) peak electromyographic activity of GG (GGEMG) and of DEMG, frequency discharge, and arterial blood pressure (BP) and heart rate. Prior injection of OT antagonist [d-(CH2)5,Tyr(Me)2,Orn8]-vasotocin intracisternally or blockade of OT receptors in the pre-BötC region with OT antagonist l-368,899, diminished GGEMG and DEMG responses and blunted the increase in BP and heart rate to PVN stimulation. These data show that PVN stimulation affects central regulatory mechanisms via the pre-BötC region controlling both respiratory and cardiovascular functions. The parallel changes induced by PVN stimulation were mediated mainly through an OT-OT receptor signaling pathway.

NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex

2005 ◽  
Vol 288 (6) ◽  
pp. R1707-R1715 ◽  
Author(s):  
John M. Makeham ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Substance P ◽  
Phrenic Nerve ◽  
Receptor Activation ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Nk1 Receptor ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Phrenic Nerve Activity ◽  
Arterial Blood

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5–11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O2)11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O2)11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

scholarly journals Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats

2015 ◽  
Vol 309 (5) ◽  
pp. H880-H887 ◽  
Author(s):  
Michael J. Huber ◽  
Rupsa Basu ◽  
Cassie Cecchettini ◽  
Adolfo E. Cuadra ◽  
Qing-Hui Chen ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Mrna Levels ◽  
Ros Production ◽  
Activator Protein 1 ◽  
Sprague Dawley ◽  
Neurogenic Hypertension ◽  
Napdh Oxidase ◽  
Arterial Blood ◽  
Sd Rats ◽  
Oxide Synthase

Previous studies have indicated that hyperactivity of brain prorenin receptors (PRR) is implicated in neurogenic hypertension. However, the role of brain PRR in regulating arterial blood pressure (ABP) is not well understood. Here, we test the hypothesis that PRR activation in the hypothalamic paraventricular nucleus (PVN) contributes to increased sympathetic nerve activity (SNA). In anaesthetized adult Sprague-Dawley (SD) rats, bilateral PVN microinjection of human prorenin (2 pmol/side) significantly increased splanchnic SNA (SSNA; 71 ± 15%, n = 7). Preinjection of either prorenin handle region peptide, the PRR binding blocker (PRRB), or tiron (2 nmol/side), the scavenger of reactive oxygen species (ROS), significantly attenuated the increase in SSNA (PRRB: 32 ± 5% vs. control, n = 6; tiron: 8 ± 10% vs. control, n = 5; P < 0.05) evoked by prorenin injection. We further investigated the effects of PRR activation on ROS production as well as downstream gene expression using cultured hypothalamus neurons from newborn SD rats. Incubation of brain neurons with human prorenin (100 nM) dramatically enhanced ROS production and induced a time-dependent increase in mRNA levels of inducible nitric oxide synthase (iNOS), NAPDH oxidase 2 subunit cybb, and FOS-like antigen 1 (fosl1), a marker for neuronal activation and a component of transcription factor activator protein-1 (AP-1). The maximum mRNA increase in these genes occurred 6 h following incubation (iNOS: 201-fold; cybb: 2 -fold; Ffosl1: 11-fold). The increases in iNOS and cybb mRNA were not attenuated by the AT1 receptor antagonist losartan but abolished by the AP-1 blocker curcumin. Our results suggest that PVN PRR activation induces sympathoexcitation possibly through stimulation of an ANG II-independent, ROS-AP-1-iNOS signaling pathway.

scholarly journals In Vivo Discharge Properties of Hypothalamic Paraventricular Nucleus Neurons With Axonal Projections to the Rostral Ventrolateral Medulla

2010 ◽  
Vol 103 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Qing-Hui Chen ◽  
Glenn M. Toney
Keyword(s):  
Paraventricular Nucleus ◽  
Extracellular Recording ◽  
Firing Frequency ◽  
Rostral Ventrolateral Medulla ◽  
Hypothalamic Paraventricular Nucleus ◽  
Ventrolateral Medulla ◽  
Spontaneous Discharge ◽  
Axonal Projections ◽  
Arterial Blood

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) are key components of a neural network that generates and regulates sympathetic nerve activity (SNA). Although each region has been extensively studied, little is presently known about the in vivo discharge properties of individual PVN neurons that directly innervate the RVLM. Here extracellular recording was performed in anesthetized rats, and antidromic stimulation was used to identify single PVN neurons with axonal projections to the RVLM ( n = 94). Neurons were divided into two groups that had either unbranched axons terminating in the RVLM (i.e., PVN-RVLM neurons, n = 65) or collateralized axons targeting both the RVLM and spinal cord [i.e., PVN-RVLM/intermediolateral cell column (IML) neurons, n = 29]. Many PVN-RVLM (32/65, 49%) and PVN-RVLM/IML (17/29, 59%) neurons were spontaneously active. The average firing frequency was not different across groups. Spike-triggered averaging revealed that spontaneous discharge of most neurons was temporally correlated with renal SNA (PVN-RVLM: 12/21, 57%; PVN-RVLM/IML: 6/9, 67%). Time histograms triggered by the electrocardiogram (ECG) R-wave indicated that discharge of most cells was also cardiac rhythmic (PVN-RVLM: 25/32, 78%; PVN-RVLM/IML: 10/17, 59%). Raising and lowering arterial blood pressure to increase and decrease arterial baroreceptor input caused a corresponding decrease and increase in firing frequency among cells of both groups (PVN-RVLM: 9/13, 69%; PVN-RVLM/IML: 4/4, 100%). These results indicate that PVN-RVLM and PVN-RVLM/IML neurons are both capable of contributing to basal sympathetic activity and its baroreflex modulation.

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