Reduction of catecholamine-induced cardiovascular malformations in the chick embryo with metoprolol.
It has been documented that activation of the beta 1-adrenergic receptor mechanism is directly related to cardiovascular malformations associated with the heart and great vessels of the embryonic chick. These adrenergic receptors are believed to be present and functional in the innervated and noninnervated embryonic heart at early stages of development. The present study examined the effects of four sympathomimetic cardioactive amines on chick cardiovascular morphogenesis at Hamburger and Hamilton stage 24. Special attention was directed toward understanding dopamine teratogenicity. In order of decreasing potency at the maximum teratogenic dose (dopamine greater than isoproterenol greater than epinephrine greater than norepinephrine) each drug was found capable of producing aortic arch anomalies of the third, fourth, and sixth aortic arches and ventricular septal defects (VSD). A new specific beta 1-adrenergic antagonist, metoprolol tartrate, was employed in an attempt to lower the incidence of these cardiovascular malformations. Pretreatment with this selective beta 1-blocker profoundly reduced the incidence of malformations within any amine-treated group. These experiments demonstrate that dopamine, as well as the other sympathomimetic amines, is a potent teratogen and most likely produces these cardiovascular malformations by primarily stimulating the beta 1-adrenoreceptor in the embryonic chick.
D000014:Abnormalities, Drug-Induced / Q000503:physiopathology; D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities; D018376:Cardiovascular Abnormalities; D002395:Catecholamines / Q000633:toxicity*; D002642:Chick Embryo; D004298:Dopamine / Q000633:toxicity; D004336:Drug Antagonism; D004837:Epinephrine / Q000633:toxicity; D007545:Isoproterenol / Q000633:toxicity; D008790:Metoprolol / Q000494:pharmacology*; D009638:Norepinephrine / Q000633:toxicity; D013723:Teratogens
D002395:Catecholamines; D013723:Teratogens; D008790:Metoprolol; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine