Sulfuric acid induces airway hyperresponsiveness to substance P in the guinea pig.
We investigated whether sulfuric acid inhalation would cause hyperresponsiveness to substance P. Guinea pigs became dyspneic during a 1 h sulfuric 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 measured. Sulfuric acid slightly increased histamine responsiveness compared to controls. However, sulfuric acid caused a much more pronounced leftward shift in the dose response to substance P. Coadministration of the neutral endopeptidase (NEP) inhibitor, thiorphan, did not reduce sulfuric acid-related hyperresponsiveness to substance P. By 72 h, sensitization 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 substance P. Inactivation of NEP does not appear to account for this effect.
Stengel
P W
PW
Eli Lilly and Company, Pulmonary Research, Lilly Corporate Center, Indianapolis, IN 46285.
Bendele
A M
AM
Cockerham
S L
SL
Silbaugh
S A
SA
D000280:Administration, Inhalation; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D013373:Substance P / Q000494:pharmacology*; D013464:Sulfuric Acids / Q000008:administration & dosage / Q000633:toxicity*; D015244:Thiorphan / Q000494:pharmacology
D013464:Sulfuric Acids; D013373:Substance P; D006632:Histamine; D015244:Thiorphan; C033158:sulfuric acid