Acrolein increases airway sensitivity to substance P and decreases NEP activity in guinea pigs.
The effects of acrolein exposure on airway responses to intravenous substance P were determined in guinea pigs exposed to vehicle or 1.6 ppm acrolein for 7.5 h on 2 consecutive days and examined 1, 4, 8, 15, and 28 days after exposure by use of pulmonary mechanics and bronchoalveolar lavage (BAL). Lung, trachea, liver, and BAL fluid were also assayed for neutral endopeptidase (NEP) activity 1, 7, and 28 days after exposure. Pulmonary inflammation and epithelial damage were prominent 1 day after acrolein exposure. NEP activity was decreased in the lungs, trachea, and liver 1 and 7 days after acrolein. Twenty-eight days after exposure, NEP activity in the lungs and liver was not significantly different in vehicle- and acrolein-exposed guinea pigs but was still reduced in tracheal tissue. The BAL NEP activity in acrolein-exposed guinea pigs was approximately twice that of vehicle control guinea pigs at all three time points. Acrolein caused a prolonged increase in airway sensitivity to substance P. Experiments performed in the presence of thiorphan suggested that the acrolein-induced reduction in NEP may contribute to increased airway sensitivity to aerosolized substance P, but the increase in airway sensitivity to intravenous substance P may occur by additional mechanisms.
Turner
C R
CR
Pulmonary Pharmacology Section, ICI Americas, Inc., Wilmington, Delaware 19897.
Stow
R B
RB
Hubbs
S J
SJ
Gomes
B C
BC
Williams
J C
JC
D000171:Acrolein / Q000633:toxicity*; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000473:pathology; D004351:Drug Resistance; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012137:Respiratory System / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D015244:Thiorphan / Q000494:pharmacology
D000336:Aerosols; D011506:Proteins; D013373:Substance P; D000171:Acrolein; D015244:Thiorphan; D015260:Neprilysin