scholarly journals Combined V1a and V1b Receptor Activation Within the Paraventricular Nucleus Contributes to Sympathoexcitation and Hypertension in Rats Exposed to Chronic Mild Unpredictable Stress

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Dragana Komnenov ◽  
Harrison Quaal ◽  
Noreen Felice Rossi
Keyword(s):  
Paraventricular Nucleus ◽  
Receptor Activation ◽  
V1b Receptor

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.

Agonist and hypertonic saline-induced trafficking of the NK3-receptors on vasopressin neurons within the paraventricular nucleus of the hypothalamus

2006 ◽  
Vol 290 (5) ◽  
pp. R1242-R1250 ◽  
Author(s):  
Gwendolen E. Haley ◽  
Francis W. Flynn
Keyword(s):  
Paraventricular Nucleus ◽  
Receptor Activation ◽  
Receptor Internalization ◽  
Endogenous Ligand ◽  
Intraventricular Injections ◽  
Membrane Bound ◽  
Neurokinin 3 Receptor ◽  
Vasopressin Neurons ◽  
Local Release ◽  
Vasopressinergic Neurons

The neurokinin 3 receptor (NK3R) is colocalized with vasopressinergic neurons within the hypothalamic paraventricular nucleus (PVN) and intraventricular injections of NK3R agonists stimulate vasopressin (VP) release. Our objectives were to test the hypotheses that intraventricular injections of the selective NK3R agonist, succinyl-[Asp6, N-Me-Phe8] substance P (senktide), activate NK3R expressed by vasopressinergic neurons within the PVN, and see whether NK3R expressed by vasopressinergic neurons in the PVN are activated by hyperosmolarity. NK3R internalization was used as a marker of receptor activation. Immunohistochemistry revealed that NK3Rs were membrane-bound on VP immunoreactive neurons in control rats. Following senktide injection, there was a significant increase in the appearance of NK3R immunoreactivity within the cytoplasm and a morphological rearrangement of the dendrites, indicating receptor internalization, which was reversible. Furthermore, pretreatment with a selective NK3R antagonist, SB-222200, blocked the senktide-induced VP release and internalization of the NK3R in the PVN. These results show that the trafficking of the NK3R is due to ligand binding the NK3R. In a subsequent experiment, rats were administered intragastric loads of 2 or 0.15 M NaCl, and NK3R immunohistochemistry was used to track activation of the receptor. In contrast to control rats, 2 M NaCl significantly increased plasma VP levels and caused the internalization of the NK3R on VP neurons. Also, NK3R immunoreactivity was located in the nuclei of vasopressinergic neurons after senktide and 2 M NaCl treatment. These results show that hyperosmolarity stimulates the local release of an endogenous ligand in the PVN to bind to and activate NK3R on vasopressinergic neurons.

scholarly journals Salt-induced sympathoexcitation involves vasopressin V1a receptor activation in the paraventricular nucleus of the hypothalamus

2015 ◽  
Vol 309 (11) ◽  
pp. R1369-R1379 ◽  
Author(s):  
Natalia Ribeiro ◽  
Helena do Nascimento Panizza ◽  
Karoline Martins dos Santos ◽  
Hildebrando C. Ferreira-Neto ◽  
Vagner Roberto Antunes
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Paraventricular Nucleus ◽  
Receptor Activation ◽  
High Salt ◽  
Male Rats ◽  
Plasma Sodium ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet

A high-salt diet can lead to hydromineral imbalance and increases in plasma sodium and osmolality. It is recognized as one of the major contributing factors for cardiovascular diseases such as hypertension. The paraventricular nucleus (PVN) plays a pivotal role in osmotically driven sympathoexcitation and high blood pressure, the precise mechanisms of which are not fully understood. Recent evidence indicates that AVP released from magnocellular neurons might be involved in this process. Using a combination of in vivo and in situ studies, we sought to investigate whether AVP, acting on PVN neurons, can change mean arterial pressure (MAP) and sympathetic nerve activity (SNA) in euhydrated male rats. Furthermore, we wanted to determine whether V1a receptors on PVN neurons would be involved in salt-induced sympathoexcitation and hypertension. In rats, 4 days of salt loading (NaCl 2%) elicited a significant increase in plasma osmolality (39 ± 7 mosmol/kgH2O), an increase in MAP (26 ± 2 mmHg, P < 0.001), and sympathoexcitation compared with euhydrated rats. Microinjection of AVP into the PVN of conscious euhydrated animals (100 nl, 3 μM) elicited a pressor response (14 ± 2 mmHg) and a significant increase in lumbar SNA (100 nl, 1 mM) (19 ± 5%). Pretreatment with a V1a receptor antagonist, microinjected bilaterally into the PVN of salt-loaded animals, elicited a decrease in lumbar SNA (−14 ± 5%) and MAP (−19 ± 5 mmHg), when compared with the euhydrated group. Our findings show that AVP plays an important role in modulating the salt-induced sympathoexcitation and high blood pressure, via V1a receptors, within the PVN of male rats. As such, V1a receptors in the PVN might contribute to neurogenic hypertension in individuals consuming a high-salt diet.

scholarly journals Paraventricular Nucleus P2X7 Receptors Aggravate Acute Myocardial Infarction Injury via ROS-Induced Vasopressin-V1b Activation in Rats

2021 ◽  
Author(s):  
Wenjing Cheng ◽  
Yinggang Sun ◽  
Qin Wu ◽  
Kokwin Ooi ◽  
Yi Feng ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Paraventricular Nucleus ◽  
Microglial Activation ◽  
Myocardial Injury ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidase Inhibitor ◽  
P2x7 Receptors ◽  
Sympathetic Hyperactivity ◽  
V1b Receptor ◽  
Vasopressinergic Neurons

AbstractThe present study was designed to investigate the mechanisms by which P2X7 receptors (P2X7Rs) mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus (PVN) of the hypothalamus of rats with acute myocardial ischemia (AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG (brilliant blue G, a P2X7R antagonist), nelivaptan (a vasopressin V1b receptor antagonist), or diphenyleneiodonium (DPI) [an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species (ROS) and NADPH oxidase 2 (NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes. Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine (AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron-V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.

scholarly journals Korean red ginseng excitation of paraventricular nucleus neurons via non-N-methyl-D-aspartate glutamate receptor activation in mice

2018 ◽  
Vol 19 (2) ◽  
pp. 172
Author(s):  
Yiming Shen ◽  
Janardhan P. Bhattarai ◽  
Soo Joung Park ◽  
Gyu Seung Lee ◽  
Pan Dong Ryu ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Paraventricular Nucleus ◽  
Receptor Activation ◽  
Red Ginseng ◽  
Korean Red Ginseng

VR1 Receptor Activation Induces Glutamate Release and Postsynaptic Firing in the Paraventricular Nucleus

2004 ◽  
Vol 92 (3) ◽  
pp. 1807-1816 ◽  
Author(s):  
De-Pei Li ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Paraventricular Nucleus ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Ruthenium Red ◽  
Thoracic Spinal Cord ◽  
Synaptic Inputs ◽  
Postsynaptic Currents ◽  
Thoracic Spinal ◽  
Immunofluorescence Labeling

Neurons in the paraventricular nucleus (PVN) are important in regulating autonomic function through projections to the brain stem and spinal cord. Although the vanilloid receptors (VR1) are present in the PVN, their physiological function is scarcely known. In this study, we determined the role of VR1 receptors in the regulation of synaptic inputs and the excitability of spinally projecting PVN neurons. Whole cell patch-clamp recordings were performed on the PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Capsaicin significantly increased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) without changing the amplitude and decay time constant of mEPSCs. On the other hand, capsaicin had no effect on GABAergic miniature inhibitory postsynaptic currents (mIPSCs). The effect of capsaicin on mEPSCs was abolished by a specific VR1 antagonist, iodo-resiniferatoxin (iodo-RTX), or ruthenium red. Importantly, iodo-RTX per se significantly reduced the amplitude of evoked EPSCs and the frequency of mEPSCs. Removal of extracellular Ca2+, but not Cd2+ treatment, also eliminated the effect of capsaicin on mEPSCs. Furthermore, capsaicin caused a large increase in the firing rate of PVN neurons, and such an effect was abolished in the presence of ionotropic glutamate receptor antagonists. Additionally, the double-immunofluorescence labeling revealed that all of the VR1 immunoreactivity was colocalized with a presynaptic marker, synaptophysin, in the PVN. Thus this study provides the first evidence that activation of VR1 receptors excites preautonomic PVN neurons through selective potentiation of glutamatergic synaptic inputs. Presynaptic VR1 receptors and endogenous capsaicin-like substances in the PVN may represent a previously unidentified mechanism in hypothalamic regulation of the autonomic nervous system.

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