ArticlePloS one2011
Caffeine acts via A1 adenosine receptors to disrupt embryonic cardiac function.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Deciphering epigenetic regulation in cardiac developmental toxicity: Mechanisms and implications (Review).Molecular medicine reports · 2026Review
- Environmental Signals.Advances in experimental medicine and biology · 2024Article
- Caffeine: cardiorespiratory effects and tissue protection in animal models.Experimental animals · 2021Review
- Transient Disruption of Adenosine Signaling During Embryogenesis Triggers a Pro-epileptic Phenotype in Adult Zebrafish.Molecular neurobiology · 2018Article
- Long-term consequences of disrupting adenosine signaling during embryonic development.Molecular aspects of medicine · 2017Review
- Impaired novelty acquisition and synaptic plasticity in congenital hyperammonemia caused by hepatic glutamine synthetase deficiency.Scientific reports · 2017Article
- Caffeine and cardiovascular diseases: critical review of current research.European journal of nutrition · 2016Review
- Control of the heart rate of rat embryos during the organogenic period.Hypoxia (Auckland, N.Z.) · 2016Article
- Cardiac purinergic signalling in health and disease.Purinergic signalling · 2015Review
- Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Article
- Effect of Caffeine Chronically Consumed During Pregnancy on Adenosine AJournal of caffeine research · 2014Article
- Acid-sensing hypothalamic neurons controlling arousal.Cellular and molecular neurobiology · 2014Review
- Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.PloS one · 2014Article
- Maternal caffeine administration leads to adverse effects on adult mice offspring.European journal of nutrition · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEvidence 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
findingsEffects 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.
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