Analysis of the cardiotoxic effect of isoproterenol in chick embryo.
Intraamnial administration of isoproterenol (IPRO) to chick embryo induces different types of pathological changes of the myocardial and liver tissue: their character depends upon the developmental period during which the drug was administered. Analysis of the embryotoxic effect of IPRO has revealed that the time-course of in vivo uptake of [3H]IPRO by the developing heart appears to present the same pattern as the embryonic liver tissue; both peak values (10 min and 6 h after injection) were, however, significantly higher in the liver as compared with the myocardium. IPRO is rapidly metabolized to 3-o-methyl-IPRO; the proportion of this fraction in both organs represents approximately 40% of total radioactivity as early as 5 min after administration. Intraamnial administration of IPRO significantly increases the cAMP content in the myocardium; dibutyryl cAMP-induced myocardial lesions occurred, however, only occasionally and in comparison with IPRO they were significantly less pronounced. The cardiotoxic effect of IPRO can be significantly reduced by beta-blockade; calcium antagonist, verapamil, was found to have no protective effect. Our results suggest that the following factors may participate in the IPRO-induced embryotoxicity: (1) IPRO, (2) its toxic metabolites, (3) cAMP.
D000042:Absorption; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced*; D002642:Chick Embryo; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use
D011433:Propranolol; D014700:Verapamil; D007545:Isoproterenol