Ontogeny of humoral heart rate regulation in the embryonic mouse.
Catecholamines, acetylcholine, and adenosine are known to influence cardiac function, yet the effects of these agents on mammalian embryonic myocardium are largely unknown. To address this issue, we compared the chronotrophic effects of adenosinergic, adrenergic, and muscarinic agents on cultured murine embryos from postcoital day (PC) 8.0, when the fusing heart tubes first begin to beat, to PC 14, when cardiogenesis is essentially complete. At PC 8.0 and older, A(1)-adenosine receptor (A(1)AR) activation significantly decreased heart rates. Adrenergic stimulation caused modest increases in heart rates (145-155% of baseline) beginning at PC 9.0. Muscarinic activation decreased heart rates only after PC 13. When receptor gene expression was examined, A(1)ARs and beta(1)ARs were expressed in isolated hearts as early as PC 9.0, and beta(2)ARs and m(2)-muscarinic receptor genes were expressed at PC 11.0. These results identify the adenosinergic system as the earliest and most potent regulator of embryonic cardiac function and show that prenatal responsiveness to catecholamines and acetylcholine develops at later embryonic stages.
Porter
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GA
Division of Cardiology, Yale University School of Medicine, 464 Congress Ave., New Haven, CT 06520, USA.
Rivkees
S A
SA
D000241:Adenosine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018663:Adrenergic Agents / Q000378:metabolism / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D018678:Cholinergic Agents / Q000378:metabolism / Q000494:pharmacology*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009200:Myocardial Contraction; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism
D018663:Adrenergic Agents; D018678:Cholinergic Agents; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; D000241:Adenosine