Relation between functional maturation of cervical sympathetic innervation and ontogeny of alpha-noradrenergic smooth muscle contraction in the rat.

Abstract The functional ontogeny of a sympathetic neuroeffector system consisting of postganglionic neuron and smooth muscle end organ was studied in vivo in the rat at selected times from birth through 75 days of age. The maximum noradrenergic contractile response of the smooth muscle (Mu¨ller's) component of the levator palpebrae was assessed with the directly acting agonist, methoxamine. The functional capacity of the nerve terminals innervating the muscle to evoke contraction was determined by displacing their endogenous noradrenaline with tyramine. The integrity of the pathway from preganglionic axon to end organ was tested by stimulating the preganglionic axons electrically. The smooth muscle contractile response to methoxamine increased in a step-wise fashion through the 20th postnatal day. On day 1, the response was 2% of the mature (70–75 day) value. The response increased to 17% on day 4, and remained at this level through the 9th day. A second increase to 32% occurred between the 10th and 12th day, and there was no further increase through the 19th day. Responses increased to 64% of the mature value by the 45–50th postnatal day. Responses to tyramine were always comparable to those evoked by methoxamine. Electrical stimulation of the preganglionic nerve failed to evoke contractions on days 1 and 4, but from day 8 on, responses to preganglionic stimulation, tyramine and methoxamine were comparable. Decentralization of the superior cervical ganglion on the 1st postnatal day decreased the response to endogenously-released nerve terminal noradrenaline by 25% at 18–19 days postnatally and the deficit persisted to maturity. In contrast, the response to direct noradrenergic stimulation was attenuated at 70–75 days postnatally, but not at 18–19 and 45–50 days. Sham operation itself significantly decreased responses to methoxamine and tyramine at 18–19 and 45–50 days of age, but not at 70–75 days. The following conclusions were reached. Functional capacity of the postganglionic sympathetic nerve terminals develops at least as rapidly as the capacity of the smooth muscle to respond directly to α-noradrenergic stimulation. The connection between central nervous system and postganglionic sympathetic neuron is not required to initiate functional maturation of the neuron, postsynaptic α-noradrenergic receptors or post-receptor smooth muscle contractile elements. After ganglionic neurotransmission is established, there is a significant, though modest, transynaptically mediated contribution to overall functional maturation of postganglionic neuron and end organ. The maturational deficit (about 25%) which follows decentralization of the postganglionic neuron on the 1st postnatal day is manifest first in the sympathetic nerve terminal; this, in turn, appears to lead to a deficit in smooth muscle response to direct α-noradrenergic stimulation. Thus, decentralization in the neonate prior to establishment of ganglionic neurotransmission leads to subsensitivity of α-noradrenergic end organ response while decentralization in mature animals is known to result in supersensitivity. Since the contribution of neural, transynaptic factors to maturation was modest in this sympathetic neuroeffector system, consideration is given to the possibility that humoral factors such as thyroid and growth hormone play major roles in development of the postganglionic neuron and end organ.