Changes in sensitivity of rat heart to norepinephrine and isoproterenol during pre- and postnatal development and its relation to sympathetic innervation.

Possible correlation between sympathetic innervation and sensitivity to adrenergic agonists was examined with developing rat hearts. Chronotropic responses of right atria to tyramine (TYR) was absent until the 15th day of gestation. After the 17th day of gestation, the maximum chronotropism by TYR was equal to that by norepinephrine (NE), indicating the development of functional sympathetic innervation to sinus node during this period. In ventricle, TYR responsiveness was low at birth and increased with age, indicating an increased sympathetic innervation during early postnatal period. Both in atria and ventricle, sensitivity to NE was high in early fetal ages followed by a 10-fold decrease after the onset of sympathetic innervation. Similar changes were observed in the sensitivity to isoproterenol, suggesting the postjunctional nature of this sensitivity change. There was no difference in sensitivities to dibutyryl cyclic AMP and forskolin between ventricles from 1-day- and 1-week-old neonates, suggesting changes in beta-receptor-adenylate cyclase system as a cause of this sensitivity change. The observed parallelism between functional sympathetic innervation and postjunctional sensitivity changes supports the hypothesis that sympathetic nerve exerts trophic influence upon cardiac muscle development to regulate the sensitivity to agonists.