Parasympathetic excitation of sympathetic innervation after cholinesterase inhibition.

1. Orbital parasympathetic innervation normally provides prejunctional muscarinic inhibition of sympathetic neurotransmission without activation of excitatory muscarinic receptors located on the innervated smooth muscle. The present study examines the role of acetylcholinesterase (AChE) in limiting the effects of parasympathetically released acetycholine to prejunctional receptors. 2. Urethane anaesthetized rats were placed in a stereotaxic frame, and parasympathetic activation was achieved by electrical stimulation (20 Hz, < 2.0 V) of the ipsilateral superior salivatory nucleus. Drugs were administered through a femoral venous cannula. Superior tarsal smooth muscle responses were measured by recording eyelid tension. 3. Parasympathetic stimulation alone caused a small decrease in resting tension; previous studies have shown this to be attributable to attention of resting sympathetic tone. Parasympathetic activation following physostigmine administration, however, evoked a large contractile response. Contractions were resistant to atropine but were blocked by gallamine, guanethidine, and phentolamine. 4. We conclude that AChE inhibition results in conversion of orbital parasympathetic nerve function from inhibition of sympathetic neurotransmission to smooth muscle excitation. This occurs as a result of cholinergic activation of excitatory nicotinic receptors on sympathetic varicosities, which elicit the release of noradrenaline.