Maturation of sympathetic neurotransmission in the rat heart. IV. Effects guanethidine-induced sympathectomy on neonatal development of synaptic vesicles, synaptic terminal function and heart growth.

Abstract

Sympathetic nerve input has been proposed to regulate cardiac growth and differentiation. In the present study, this hypothesis was tested by giving the neurotoxic adrenergic neuron blocking agent, guanethidine (50 mg/kg, s.c.), daily to rats for 21 consecutive days to produce long-term peripheral sympathectomy in neonatal rats. Ontogeny of the sympathetic nerve terminal was measured by the ablity of synaptic vesicle preparations to take up radiolabeled norepinephrine, and heart growth in the sympathectomized animals was monitored by organ weight as well as by RNA and protein synthesis. Guanethidine treatment produced a massive sympathectomy, as synaptic vesicle development was totally arrested; the functional consequence of this treatment was confirmed by the attenuation of chronotropic responses to tyramine, a drug which acts by displacement of norepinephrine from the noradrenergic terminal. Despite the clear-cut effectiveness of guanethidine to prevent formation of functional sympathetic innervation of the heart, no significant alterations in heart growth or RNA and protein synthetic capabilities were observed in the developing rats. These results suggest that the presence of sympathetic innervaton is not obligatory for normal growth of the heart to occur.