Antagonism of cholinergic nerve-mediated contractions by the sensory nerve inhibitory system in rat bronchi. Szarek, John L., and Beverly Spurlock. Marshall University School of Medicine, Department of Pharmacology, Huntington, WV 25704-9388
APStracts 3:0102A, 1996.
In a previous study we found that electrical field stimulation (EFS) evoked nonadrenergic noncholinergic nerve-mediated relaxation responses in bronchi isolated from Sprague-Dawley rats. The relaxation responses were attenuated by desensitization of sensory nerves by capsaicin, a result demonstrating the sensory nature of the nonadrenergic noncholinergic nerves. Little is known about the importance of this system in modulating airway responsiveness. Thus the purpose of the present study was to examine the potential functional significance of this inhibitory system in modulating contractions mediated by activation of cholinergic nerves. Since EFS of isolated airways activates all nerves in the airway segment, the first hypothesis of this study was that antagonists of the inhibitory system will potentiate contractile responses evoked by EFS. A second hypothesis was that replacement of one potential mediator, substance P, will inhibit cholinergic contractions. Segments of intrapulmonary bronchi were isolated from male Sprague Dawley rats and mounted on a myograph such that circumferential tension could be monitored. Desensitization of sensory nerves with capsaicin enhanced contractile responses to EFS without affecting contraction to exogenous acetylcholine (ACh). Similar results were obtained in airways after antagonizing NK1 receptors with RP67580, however, the NK1 antagonist had a slight inhibitory effect on ACh-induced contractions. Inhibition of cyclooxygenase with meclofenamate also enhanced contractile responses elicited by EFS without affecting ACh-induced contractions. Incubation of capsaicin-desensitized airway segments with substance P attenuated contractions evoked by an ED50 frequency of EFS by about 92% whereas contractions elicited by an ED50 concentration of exogenous ACh were not affected. Contractile responses elicited by a lower concentration of ACh were inhibited by about 50% by substance P. The inhibitory effect of substance P was blocked by RP67580, meclofenamate, and epithelial denudation. Based on these results and those of our previous study, we conclude that the sensory nerve inhibitory system modulates cholinergic contractions and thus plays a role in the regulation of airway smooth muscle tone. 

Received 15 August 1995; accepted in final form 2 February 1996.
APS Manuscript Number A897-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 24 February 96