6-Hydroxydopamine induced cardiac malformations and alterations of the autonomic nervous system in the developing...

6-Hydroxydopamine (6-OHDA) was injected into the air sac of developing chicken embryos on day E3 in order to study its effects on cardiac development both morphologically and biochemically. A dose-dependent teratogenic effect and fetotoxicity were observed in the 6-OHDA-treated embryos. Cardiac malformations, including ventricular septal lesions, detachment of the apical portions of the ventricles, cardiac hypertrophy, areas of coagulative necrosis with pyknotic nuclei and broken nuclear membranes, and swollen mitochondria were evident from gross histologic and ultrastructural examinations. A LD50 of 0.3 mg/egg on day E11 was obtained. Biochemically, 6-OHDA induced a significant dose-dependent reduction in the total cardiac choline acetyltransferase (ChAT) activities on days E8 and E11, followed by a recovery on days E15 and E20. The effects on muscarinic acetylcholine receptors (mAChRs) were less marked than on ChAT, indicating the effects on the cholinergic nervous system development are primarily presynaptic. There was a significant decrease in the level of norepinephrine (NE) and a delay in the appearance of detectable cardiac NE. It is suggested that 6-OHDA-induced cardiac malformation can be a useful model to study the mechanisms of cardiovascular development.