ACROLEIN INCREASES AIRWAY SENSITIVITY TO SUBSTANCE-P AND DECREASES NEP ACTIVITY IN GUINEA-PIGS

The effects of acrolein exposure on airway responses to intravenous su bstance 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, an d 28 days after exposure by use of pulmonary mechanics and bronchoalve olar lavage (BAL). Lung, trachea, liver, and BAL fluid were also assay ed for neutral endopeptidase (NEP) activity 1, 7, and 28 days after ex posure. 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 afte r exposure, NEP activity in the lungs and liver was not significantly different in vehicle- and acrolein-exposed guinea pigs but was still r educed in tracheal tissue. The BAL NEP activity in acrolein-exposed gu inea pigs was approximately twice that of vehicle control guinea pigs at all three time points. Acrolein caused a prolonged increase in airw ay sensitivity to substance P. Experiments performed in the presence o f thiorphan suggested that the acrolein-induced reduction in NEP may c ontribute to increased airway sensitivity to aerosolized substance P, but the increase in airway sensitivity to intravenous substance P may occur by additional mechanisms.