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Embryos lacking A1ARs were markedly growth retarded following intrauterine hypoxia exposure. Studies of mice selectively lacking A1AR in the heart identify the heart as a key site of adenosine's embryo-protective effects. Studies of isolated embryos showed that adenosine plays a key role in modulating embryo cardiac function, especially in the setting of hypoxia. When pregnant mice were treated during embryogenesis with the adenosine antagonist caffeine, adult mice had abnormal heart function. Adenosine acts via A1ARs to play an essential role in protecting the embryo against intrauterine stress, and adenosine antagonists, including caffeine, may be an unwelcome exposure for the embryo.<\/jats:p>","DOI":"10.1161\/atvbaha.111.226811","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T20:49:32Z","timestamp":1331758172000},"page":"851-855","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Regulation of Cardiovascular Development by Adenosine and Adenosine-Mediated Embryo Protection"],"prefix":"10.1161","volume":"32","author":[{"given":"Scott A.","family":"Rivkees","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Wendler","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Yale Child Health Research Center, Yale University School of Medicine, New Haven, CT."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","first-page":"1","article-title":"Introduction to adenosine receptors as therapeutic targets","author":"Jacobson KA","year":"2009","unstructured":"Jacobson KA . 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