Schematic of influences of adenosine and hypoxia on embryonic heart rate regulation.
Hypoxia induces increased levels of adenosine, which in turn activate A1ARs to lower heart rate. Reduction in heart rate will affect embryonic tissue perfusion, which in turn will influence embryonic development. At E9.5, effects of hypoxia on heart rate appear to be exclusively mediated via A1ARs. At E12.5, hypoxia also can influence heart rate independent of A1ARs. Caffeine, an adenosine antagonist, will perturb this physiological cascade.