MATURATION OF SYMPATHETIC NEUROTRANSMISSION IN THE RAT-HEART .9. DEVELOPMENT OF TRANSSYNAPTIC REGULATION OF CARDIAC ADRENERGIC SENSITIVITY

Abstract

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 site; 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 bindng sites. These data in the adult agree with classical transsynaptic modulation of adrenergic postsynaptic reactivity. 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-4th wk. 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.