Analysis of preganglionic nerve evoked cholinergic contractions of the guinea pig bronchus

We compared cholinergic bronchial muscle contractions induced by vagus nerve (preganglionic) stimulation (VNS) with those induced by electrical field (postganglionic) stimulation (EFS). When normalized to their respective maximum response, the frequency-response curves (10 s trains) between 4 and 16 Hz were similar between VNS and EFS; however, at frequencies of 0.1-2 Hz, and at frequencies greater than 32 Hz, the VNS contractions were significantly less than EFS. When contractions elicited by 100 pulses were examined, it was found that the responses to VNS were maximal at 10-30 Hz then declined significantly to 82-35% of maximal between 40 and 200 Hz, whereas the response to EFS was essentially unchanged at frequencies up to 60 Hz and declined only to 72% of maximal up to 200 Hz. At frequencies as low as 20 Hz, the contractions evoked by VNS faded to 45 +/- 9% of the peak contraction during 60 sec of continuous stimulation, whereas those evoked by 60 sec continuous EFS remained constant. This fade observed during prolonged VNS was not blocked by the antagonists, pirenzepine and AFDX-116, at concentrations selective for M1 and M2 muscarinic receptors, respectively; nor was the fade blocked by pre-treatment with indomethacin, propranolol, phentolamine, or choline. At frequencies greater than 10 Hz, the amplitude of the preganglionic compound action potential also faded during repetitive stimulation. The results support the hypothesis that the airway ganglion neurons innervating guinea pig bronchial smooth muscle effectively filter preganglionic stimuli, especially at low and relatively high frequencies. During continuous vagus nerve stimulation, preganglionic mechanisms may also play a role in limiting the ultimate output of airway ganglia.