Alpha-naphthylthiourea (ANTU) protects against hyperoxic depression of pulmonary serotonin uptake

To evaluate whether alpha-naphthylthioura (ANTU) protects against hyperoxic injury to the pulmonary endothelium, we monitored survival and serotonin uptake by the lungs of ANTU-treated rats (5 mg/kg) and Tween 80-treated control rats exposed to 100% O2 or air at 1 atmosphere absolute. Exposure to 100% O2 for 24 h or 48 h significantly depressed serotonin uptake in control rats. Serotonin uptake in ANTU-treated rats compared with that in control rats exposed to air for 24 or 48 h was also significantly depressed. However, serotonin uptake by the lungs of ANTU-treated rats exposed to 100% O2 for 48 h was significantly greater than uptake by control lungs similarly exposed to O2. Nine of 14 ANTU-treated rats were alive after 7 days of exposure to 100% O2, and serotonin uptake by the lungs of survivors had returned to control values (3.29 +/- 0.25). In contrast, only 1 of 14 control rats survived and serotonin uptake was 1.17 in this lone survivor. These results indicate that ANTU injuries pulmonary endothelial cells but protects against subsequently hyperoxic injury. This protection may account for the reduced mortality in ANTU-treated rats exposed to hyperoxia.