AIRWAY HYPERRESPONSIVENESS TO NEUROKININ-A AND BRADYKININ FOLLOWING MYCOPLASMA-PNEUMONIAE INFECTION ASSOCIATED WITH REDUCED EPITHELIAL NEUTRAL ENDOPEPTIDASE

To determine whether mycoplasma infection produces airway hyperrespons iveness to tachykinins and bradykinin and, if so, to elucidate the rol e of neutral endopeptidase (NEP), isolated hamster tracheal segments w ere studied under isometric conditions in vitro. Nasal inoculation wit h Mycoplasma pneumoniae potentiated contractile responses to neurokini n A and bradykinin, causing a leftward shift of the dose-response curv es to a lower concentration by 1 log unit for each agonist. whereas th ere was no response with acetylcholine. Pretreatment of tissues with t he NEP inhibitor phosphoramidon augmented neurokinin A- and bradykinin -induced contractions in saline-treated control tissues, but did not f urther potentiate the responsiveness in M. pneumoniae-infected tissues . NEP activity in the tracheal epithelium, but not in epithelium-denud ed tissues, was decreased in infected animals. These results suggest t hat M. pneumoniae infection causes airway bronchoconstrictor hyper-res ponsiveness to neurokinin A and bradykinin and that this effect may be associated with an inhibition of epithelial NEP activity.