Document Detail


An Essential role for DeltaFosB in the median preoptic nucleus in the sustained hypertensive effects of chronic intermittent hypoxia.
MedLine Citation:
PMID:  22689746     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the main clinical features of obstructive sleep apnea is sustained hypertension and elevated sympathetic activity during waking hours. Chronic intermittent hypoxia (CIH), animal model of the hypoxemia associated with obstructive sleep apnea, produces a similar sustained increase in blood pressure. This study determined the role of ΔFosB in the median preoptic nucleus (MnPO) in the sustained increase in mean arterial pressure associated with CIH. Rats were injected in the MnPO with viral vectors that expressed green fluorescent protein alone or green fluorescent protein plus a dominant-negative construct that inhibits the transcriptional effects of ΔFosB. In green fluorescent protein-injected rats and uninjected controls, 7-day exposure to CIH increased mean arterial pressure by 7 to 10 mm Hg during both intermittent hypoxia exposure and normoxia. Dominant-negative inhibition of MnPO ΔFosB did not affect changes in mean arterial pressure during intermittent hypoxia exposure but significantly reduced the sustained component of the blood pressure response to CIH during the normoxic dark phase. Inhibition of MnPO ΔFosB reduced the FosB/ΔFosB staining in the paraventricular nucleus and rostral ventrolateral medulla but not the nucleus of the solitary tract. PCR array analysis identified 6 activator protein 1-regulated genes expressed in the MnPO that were increased by CIH exposure, ace, ace2, nos1, nos3, prdx2, and map3k3. Dominant-negative inhibition of ΔFosB in the MnPO blocked increased expression of each of these genes in rats exposed to CIH except for Prdx2. ΔFosB may mediate transcriptional activity in MnPO necessary for sustained CIH hypertension, suggesting that neural adaptations may contribute to diurnal hypertension in obstructive sleep apnea.
Authors:
J Thomas Cunningham; W David Knight; Steven W Mifflin; Eric J Nestler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-06-11
Journal Detail:
Title:  Hypertension     Volume:  60     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-09-07     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  179-87     Citation Subset:  IM    
Affiliation:
Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA. Tom.Cunningham@unthsc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / genetics,  metabolism,  physiopathology*
Chronic Disease
Dependovirus / genetics
Gene Expression Profiling
Genetic Vectors / genetics
Green Fluorescent Proteins / genetics,  metabolism
Heart Rate / genetics,  physiology
Hypertension / genetics,  physiopathology*
Immunohistochemistry
Male
Microscopy, Fluorescence
Nitric Oxide Synthase Type I / genetics
Nitric Oxide Synthase Type III / genetics
Oligonucleotide Array Sequence Analysis
Peptidyl-Dipeptidase A / genetics
Peroxiredoxins / genetics
Preoptic Area / metabolism,  physiopathology*
Proto-Oncogene Proteins c-fos / genetics,  metabolism,  physiology*
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Transduction, Genetic
Grant Support
ID/Acronym/Agency:
P01 HL088052/HL/NHLBI NIH HHS; P01HL-88052/HL/NHLBI NIH HHS; R01 HL062579/HL/NHLBI NIH HHS; R01 MH-51399/MH/NIMH NIH HHS; R01 MH051399/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Fosb protein, rat; 0/Proto-Oncogene Proteins c-fos; 147336-22-9/Green Fluorescent Proteins; EC 1.11.1.15/PRDX2 protein, human; EC 1.11.1.15/Peroxiredoxins; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos1 protein, rat; EC 1.14.13.39/Nos3 protein, rat; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2
Comments/Corrections

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