NOREPINEPHRINE-INDUCED AND ISOPROTERENOL-INDUCED CHANGES IN CARDIAC CONTRACTILITY AND CYCLIC ADENOSINE 3'/5'-MONOPHOSPHATE LEVELS DURING EARLY DEVELOPMENT OF EMBRYONIC CHICK

Abstract

Changes in contractility and cyclic[c]AMP levels in response to norepinephrine and isoproterenol were monitored in isolated 4 day old (noninnervated) and 7 day old (innervated) embryonic hearts to determine whether a relationship between .beta.-adrenergic receptor, adenylate cyclase and altered cardiac function was established at a very early stage in embryonic development before innervation takes place. Norepinephrine and isoproterenol promoted rapid time- and dose-dependent rises in cAMP levels which were greater in the 4 day old hearts. These increases paralleled observed functional alterations within a specific range of drug concentrations and time. The elevation of cAMP levels and effect on cardiac function produced by isoproterenol (10-7 M) were blocked by propranolol (10-6 M). Dissociations between changes in tissue cAMP levels and cardiac function were also uncovered. Maximal increases in contractility were achieved with lower drug concentrations than were required to promote maximal accumulation of cAMP. Relatively high concentrations of norepinephrine or isoproterenol were less effective than lower concentrations in stimulating contractility but were more effective in promoting cAMP accumulation. Both cardiac .beta. receptors and adenylate cyclase were present and functionally related early in embryogenesis before sympathetic innervation occurred and cAMP accumulation was associated with modulation of contractile activity within a certain concentration range and time course.