Document Detail


High oxygen prevents fetal lethality due to lack of catecholamines.
MedLine Citation:
PMID:  18635452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at embryonic day (E)13.5-14.5, they resemble wild-type (wt) fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial detachment, and death with vascular congestion, hemorrhage, and edema. At E12.5, before the appearance of morphological deficits, catecholamine-deficient fetuses are preferentially killed by experimentally induced hypoxia and have lower tissue Po(2) levels than wt siblings. By microarray analysis (http://www.ncbi.nlm.nih.gov/geo; accession no. GSE10341), hypoxia-inducible factor-1 target genes are induced to a greater extent in null fetuses than in wt siblings, supporting the notion that mutants experience lower oxygen tension or have an enhanced response to hypoxia. Hypoxia induces a 13-fold increase in plasma norepinephrine levels, which would be expected to increase heart rate, thereby improving oxygen delivery in wt mice. Surprisingly, increasing maternal oxygen (inspired O(2) 33 or 63%) prevents the effects of catecholamine deficiency, restoring heart rate, myocardial tissue, and survival of Th null fetuses to wt levels. We suggest that norepinephrine mediates fetal survival by maintaining oxygen homeostasis.
Authors:
Margie A Ream; Rashmi Chandra; Mary Peavey; Alisa M Ray; Suzanne Roffler-Tarlov; Hyung-Gun Kim; William C Wetsel; Howard A Rockman; Dona M Chikaraishi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-16
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  295     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-08     Completed Date:  2008-10-17     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R942-53     Citation Subset:  IM    
Affiliation:
Dept. of Neurobiology, Box 3209, Duke Univ. Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / mortality,  therapy*
Bradycardia / mortality,  therapy
Disease Models, Animal
Female
Fetal Death / prevention & control
Gene Expression Regulation, Developmental
Heart Rate
Hypoxia-Inducible Factor 1 / genetics,  metabolism
Male
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Norepinephrine / blood*,  deficiency
Oxygen / pharmacology*
Oxygen Inhalation Therapy*
Pregnancy
Survival Rate
Tyrosine 3-Monooxygenase / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
NS-22675/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 51-41-2/Norepinephrine; 7782-44-7/Oxygen; EC 1.14.16.2/Tyrosine 3-Monooxygenase
Comments/Corrections

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