| Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats. | |
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MedLine Citation:
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PMID: 19020286 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the nucleus ambiguous (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3-4 mo) were exposed to room air (RA) or CIH for 35-50 days (n = 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (-200 microm to +200 microm relative to caudal end of area postrema; n = 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of -800, -400, 0, +400, and +800 microm relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH 1) HR responses to microinjection of AMPA into the left NA were reduced (RA -290 +/- 30 vs. CIH -227 +/- 15 beats/min, P < 0.05); 2) HR responses to microinjection of NMDA into the left NA were reduced (RA -302 +/- 16 vs. CIH -238 +/- 27 beats/min, P < 0.05); and 3) the number of NMDAR1, AMPA GluR1, and AMPA GluR2/3-immunoreactive cells in the NA was reduced (P < 0.05). These results suggest that degeneration of NA neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH. |
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Authors:
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Binbin Yan; Lihua Li; Scott W Harden; David Gozal; Ying Lin; William B Wead; Robert D Wurster; Zixi Jack Cheng |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-11-19 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 296 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-27 Completed Date: 2009-03-12 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R299-308 Citation Subset: IM |
Affiliation:
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Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida Parkway, Orlando, FL 32816, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / metabolism, physiopathology* Baroreflex / drug effects Blood Pressure / drug effects Brain Stem / drug effects*, metabolism, physiopathology Disease Models, Animal Down-Regulation Excitatory Amino Acid Agonists / administration & dosage, pharmacology* Heart / innervation* Heart Rate / drug effects* Microinjections Motor Neurons / drug effects, metabolism N-Methylaspartate / administration & dosage, pharmacology* Nerve Degeneration / physiopathology Rats Rats, Inbred F344 Receptors, AMPA / agonists Receptors, Glutamate / drug effects*, metabolism Receptors, N-Methyl-D-Aspartate / agonists alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / administration & dosage, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AG-021020/AG/NIA NIH HHS; HL-796369/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Excitatory Amino Acid Agonists; 0/NMDA receptor A1; 0/Receptors, AMPA; 0/Receptors, Glutamate; 0/Receptors, N-Methyl-D-Aspartate; 0/glutamate receptor ionotropic, AMPA 1; 0/glutamate receptor ionotropic, AMPA 2; 0/glutamate receptor ionotropic, AMPA 3; 6384-92-5/N-Methylaspartate; 77521-29-0/alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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