Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity to substance P.
Murlas CG; Lang Z; Williams GJ; Chodimella V
J Appl Physiol 1992 Mar; 72(3):1133-1141
Hartley-guinea-pigs were exposed to ozone (10028156) for 2 hours, and the effects on airway neutral endopeptidase (NEP) and reactivity to substance-P were studied. Intact, unanesthetized, spontaneously breathing male guinea-pigs were exposed to 3.0 parts per million ozone or to room air. Ozone exposure resulted in a substantial increase in airway reactivity to substance-P. Treatment with phosphoramidon caused a substantial increase in the substance-P reactivity of air exposed guinea-pigs. The values of NEP activities of tracheal homogenates from ozone exposed animals ranged from 16.2 to 20 nanomoles/minute milligram/protein and 22.7 to 27.5 in air exposed animals. In all animals tested, active NEP reduced substance-P reactivity after ozone exposure to preozone levels. Aerosolized phosphoramidon treatment following NEP reversed this finding. No significant influence on substance-P reactivity post ozone was demonstrated by heat inactivated NEP inhalation. A considerable decrease in substance-P reactivity produced by active NEP inhalation post ozone was noted. The authors suggest that an airway disorder associated with the loss of NEP activity can be reversed by inhaling an aerosol containing that enzyme.
NIOSH Publication; NIOSH Grant; Pulmonary system disorders; Drug therapy; Enzyme activity; Lung irritants; Laboratory animals; Inhalation studies; Airway resistance; Bronchial asthma; Respiratory system disorders
Rush-Presbyterian St. Luke Medical Center, Department of Medicine (Pulmonary), 1653 W. Congress Parkway, Chicago, IL 60612
Journal of Applied Physiology
Rush-Presbyterian St. Luke Medical Center, Department of Medicine (Pulmonary), Chicago, IL 60612