The role of β‐adrenergic activity in the production of cardiac and aortic arch anomalies in chick embryos

Abstract

The sympathomimetic amines isoproterenol, epinephrine, norepinephrine, and phenylephrine are structural derivatives of beta-phenylethylamine and have proportionately different effects on alpha- and beta-adrenergic receptors. Chick embryos in ovo were each administered a single dose of one of these compounds at concentrations ranging from 0.4 times 10(-9) to 20 times 10(-9) mol/5 mul saline during Hamburger and Hamilton stages 20-27. In other experiments embryos were pretreated with the beta-antagonist propranolol and subsequently administered isoproterenol. 743 cardiovascular anomalies were produced. The production of cardiovascular anomalies was proportional to the degree of beta-adrenergic activity of each drug. The frequency of anomalies was significantly reduced by pretreatment with propranolol. At all concentrations tested the anomaly rate was greater in chick embryos receiving an experimental compound than in controls. The general types of anomalies included aortic arch defects, ventricular septal defect, double outlet right ventricle, aortic hypoplasia, and truncus arteriosus. These results demonstrate that activation of the beta-adrenergic receptor mechanism is directly related to the cardiovascular anomalies produced in the chick embryos.

Mechanism of Nitrofen Teratogenesis

“…The resultant thyromimetic challenge could cause a precocious appearance or increase in density of ,-adrenergic receptors in the embryonic heart, as has been-demonstrated in neonatal and adult tissue (25). Heart malformations, particularly of the arterial outflow tract, have been produced in embryonic chicks via 13-adrenergic stimulation, presumably through altered cardiovascular hemodynamics (26). No link can yet be made between a thyromimetic challenge and kidney and diaphragm malformations.…”

Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation.

“…The aortic arch system of the chick differs from that of man in the following ways: bilateral brachiocephalic arteries derived from the third arch arteries (3AA) arise from the aortic root, the definitive aortic arch is right-sided and is derived from the right fourth arch artery (R4AA), the ductus arteriosus is present bilaterally (both vessels persist until hatching), and primary subclavian arteries developed from the sixteenth segmental arteries are replaced by secondary subclavian arteries arising from the 3AA in the chick embryo. '5-18 The terminology of the anomalies of the aortic arch derivatives are based on the descriptions by Rychter'7 and Hodach et al 18 Embryologic terms will be applied for the names of aortic arch artery derivatives to avoid confusion. As Rychter pointed out, in cases in which absence or anomalous origin of the right subclavian artery is associated with an interrupted right aortic arch, it is difficult to determine whether R3AA or R4AA is absent.…”

Potentiating Effects of Verapamil on Cardiovascular Teratogenicity of Phenobarbital in the Chick Embryos

“…At this time a ventral incision was carefully made ex posing abdominal and thoracic contents. Embryos were examined for aortic arch anomalies according to previously established methods [9]. Hearts were infused with Camoy fixative (60% ethanol, 30% chloroform and 10% acetic acid) and embryos were fixed with 10% formalin for 24 h. Subsequently, em bryonic hearts were carefully dissected with straightedged microscissors under a stereomicroscope.…”

“…After eggs had been incubated for ap proximately 72 h, observation windows were made in eggshells by a technique previously described [9]. When embryos had developed to stage 24 [10], they were treated with verapamil hydrochloride (Sigma Chemical Co., St. Louis, Mo., USA) in 5 pi chick Ringer's solution (123 mM NaCl, 5 mM KC1, 1.6 mM CaCL).…”