Tachykinins and Pulmonary Edema After Acute Phosgene Exposure in Guinea Pigs

We have examined the role of tachykinins, substance P, and neurokinin A in phosgene-induced pulmonary edema. Guinea pigs were exposed to air or to 50, 200, or 500 mg/m 3 phosgene (CG) for 10 min and euthanized 5, 30, 90, 180, or 240 min after exposure. Lung tissues were obtained for radioimmunoassay (RIA) and immunohistochemistry of substance P- (SP) and neurokinin A (NKA)-like immunoreactivity (LI) and for gravimetric measurements. Lung SP-LI and NKA-LI, measured by RIA, increased 30 and 90 min after 200 and 400 mg/m 3 CG exposure. Increases in lung tachykinin levels preceded lung wet weight gain due to pulmonary edema, which occurred 90 to 180 min after CG exposure. SP-LI was also detected histologically in verve varicosities in the same peribronchiolar and perivascular regions where edema was first observed 30 min after CG exposure. In related experiments, guinea pigs were given capsaicin (5- or 50-mg/kg, s.c.) 7 days before 10-min exposures to 200 mg/m 3 CG. Guinea pigs pretreated with 5 mg/kg capsaicin were depleted of tracheal, bronchial, and lung SP-LI. They had less pulmonary edema and decreased mortality after CG exposure compared to animals given the vehicle. Guinea pigs pretreated with 50 mg/kg capsaicin had reduced SP-LI and bronchial NKA-LI. They had diffuse lung edema and increased mortality after CG compared with vehicle-pretreated controls. These findings suggest that SP contributes to CG-induced pulmonary edema. NKA may partially protect lungs from the effects of CG.