Maturation of sympathetic neurotransmission in the rat heart. IX. Development of transsynaptic regulation of cardiac adrenergic sensitivity.

The number of beta adrenoceptors and the cardiac sensitivity to adrenergic stimulation increase substantially in the immediate postnatal period of the rat. To determine whether transsynaptic input influences this developmental process, the effects of a sympathomimetic and of agents which destroy noradrenergic nerve terminals on regulation of adrenergic postsynaptic sensitivity were compared in hearts from adult and developing rats. In mature animals, chronic exposure to the beta agonist isoproterenol (2.5 mg/kg s.c.) led to rapid onset (3-5 days) of chronotropic adrenergic subsensitivity accompanied by a loss of beta adrenoceptor binding sites; chemical sympathectomy by daily administration of guanethidine (50 mg/kg s.c.) or by 6-hydroxydopamine (100 mg/kg s.c. given once daily for 3 days) resulted in chronotropic adrenergic supersensitivity and increases in binding sites. These data in the adult agree with classical transsynaptic modulation of adrenergic postsynaptic reactivity. In contrast, identical drug treatments of immature rats beginning 1 day after birth failed to evoke changes in either chronotropic adrenergic sensitivity or in numbers of beta adrenoceptor binding sites until the 3rd to 4th week. Consequently, the initial development of beta adrenoceptors and responsiveness to catecholamines in the neonatal myocardium are not transsynaptically regulated; rather, other (e.g. hormonal) factors appear to control early maturation of cardiac adrenergic sensitivity.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology