Document Detail


Caffeine acts via A1 adenosine receptors to disrupt embryonic cardiac function.
MedLine Citation:
PMID:  22164264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Evidence suggests that adenosine acts via cardiac A1 adenosine receptors (A1ARs) to protect embryos against hypoxia. During embryogenesis, A1ARs are the dominant regulator of heart rate, and A1AR activation reduces heart rate. Adenosine action is inhibited by caffeine, which is widely consumed during pregnancy. In this study, we tested the hypothesis that caffeine influences developing embryos by altering cardiac function.
METHODOLOGY/PRINCIPAL FINDINGS: Effects of caffeine and adenosine receptor-selective antagonists on heart rate were studied in vitro using whole murine embryos at E9.5 and isolated hearts at E12.5. Embryos were examined in room air (21% O(2)) or hypoxic (2% O(2)) conditions. Hypoxia decreased heart rates of E9.5 embryos by 15.8% and in E12.5 isolated hearts by 27.1%. In room air, caffeine (200 µM) had no effect on E9.5 heart rates; however, caffeine increased heart rates at E12.5 by 37.7%. Caffeine abolished hypoxia-mediated bradycardia at E9.5 and blunted hypoxia-mediated bradycardia at E12.5. Real-time PCR analysis of RNA from isolated E9.5 and E12.5 hearts showed that A1AR and A2aAR genes were expressed at both ages. Treatment with adenosine receptor-selective antagonists revealed that SCH-58261 (A2aAR-specific antagonist) had no affects on heart function, whereas DPCPX (A1AR-specific antagonist) had effects similar to caffeine treatment at E9.5 and E12.5. At E12.5, embryonic hearts lacking A1AR expression (A1AR-/-) had elevated heart rates compared to A1AR+/- littermates, A1AR-/- heart rates failed to decrease to levels comparable to those of controls. Caffeine did not significantly affect heart rates of A1AR-/- embryos.
CONCLUSIONS/SIGNIFICANCE: These data show that caffeine alters embryonic cardiac function and disrupts the normal cardiac response to hypoxia through blockade of A1AR action. Our results raise concern for caffeine exposure during embryogenesis, particularly in pregnancies with increased risk of embryonic hypoxia.
Authors:
Daniela L Buscariollo; Gregory A Breuer; Christopher C Wendler; Scott A Rivkees
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-02
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-12-14     Completed Date:  2012-07-20     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e28296     Citation Subset:  IM    
Affiliation:
Section of Developmental Endocrinology and Biology, Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Air
Animals
Anoxia
Caffeine / pharmacology*
Gene Expression Regulation, Developmental*
Heart / embryology*
Heart Rate / drug effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oxygen / metabolism
Real-Time Polymerase Chain Reaction / methods
Receptor, Adenosine A1 / genetics,  metabolism*
Time Factors
Grant Support
ID/Acronym/Agency:
R01HD058086-02/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Receptor, Adenosine A1; 58-08-2/Caffeine; 7782-44-7/Oxygen
Comments/Corrections

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