SULFURIC-ACID INDUCES AIRWAY HYPERRESPONSIVENESS TO SUBSTANCE-P IN THE GUINEA-PIG

We investigated whether sulfuric acid inhalation would cause hyperresp onsiveness to substance P. Guinea pigs became dyspneic during a 1 h su lfuric acid exposure, but recovered by 24 h when they were challenged with substance P or histamine aerosols. Eight minutes after the start of challenge, animals were killed and excised lung gas volumes measure d. Sulfuric acid slightly increased histamine responsiveness compared to controls. However, sulfuric acid caused a much more pronounced left ward shift in the dose response to substance P. Coadministration of th e neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sul furic acid-related hyperresponsiveness to substance P. By 72 h, sensit ization to substance P was absent. Histological evaluation of sulfuric acid-treated lungs revealed mild alveolitis at 24 h, but not at 72 h. We conclude that sulfuric acid produces a marked sensitization to sub stance P. Inactivation of NEP does not appear to account for this effe ct.