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(Circulation Research. 2001;88:117.)
© 2001 American Heart Association, Inc.

Integrative Physiology

Embryonic Epinephrine Synthesis in the Rat Heart Before Innervation

Association With Pacemaking and Conduction Tissue Development

Steven N. Ebert, Robert P. Thompson

From the Department of Pharmacology, Georgetown University Medical Center (S.N.E.), Washington, DC, and Department of Cell Biology and Anatomy, Medical University of South Carolina (R.P.T.), Charleston, South Carolina.

Correspondence to Steven N. Ebert, PhD, Department of Pharmacology, Georgetown University Medical Center, Medical-Dental Building, SE 402, 3900 Reservoir Rd NW, Washington, DC 20007. E-mail eberts{at}gunet.georgetown.edu

Abstract—Epinephrine is a potent neurotransmitter and hormone that can influence cardiac performance beginning shortly after the first myocardial contractions occur in developing vertebrate embryos. In the present study, we provide evidence that the heart itself may produce epinephrine during embryonic development. Using antibodies that selectively recognize the catecholamine biosynthetic enzymes, tyrosine hydroxylase, dopamine ß-hydroxylase, and phenylethanolamine N-methyltransferase, we used coimmunofluorescent staining techniques to identify cardiac cells that have the capability of producing catecholamines. Initially, cells expressing catecholamine biosynthetic enzymes were found interspersed throughout the myocardium, but by embryonic day 11.5 (E11.5), they became preferentially localized to the dorsal venous valve and atrioventricular canal regions. As development proceeded, catecholamine biosynthetic enzyme expression decreased in these regions but became quite strong along the crest of the interventricular septum by E16.5. This expression pattern was also transient, decreasing in the ventricular septum by E19.5. These data are consistent with a transient and progressive association of catecholamine-producing cells within regions of the heart that become the sinoatrial node, atrioventricular node, and bundle of His. This is the first evidence demonstrating that intrinsic cardiac adrenergic cells may be preferentially associated with early pacemaking and conduction tissue development.

Key Words: phenylethanolamine N-methyltransferase • dopamine ß-hydroxylase • tyrosine hydroxylase • adrenergic

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