Exposure to hyperoxia causes lung injury, decreases active sodium transport and lung edema clearance in rats. Dopamine (DA) increases lung edema clearance by stimulating vectorial Na+ flux and Na, K-ATPase function in rat alveolar epithelium. This study was designed to test whether DA (10(-)5 M) would increase lung edema clearance in rats exposed to 100% O2 for 64 h. Active Na+ transport and lung edema clearance decreased by approximately 44% in rats exposed to acute hyperoxia (p < 0.001). DA increased lung edema clearance in room air breathing rats (from 0.50 +/- 0.02 to 0.75 +/- 0.06 ml/h) and in rats exposed to 100% O2 (from 0.28 +/- 0.03 to 0. 67 +/- 0.03 ml/h). Disruption of cell microtubular transport system by colchicine blocked the stimulatory effect of DA on active Na+ transport in control and hyperoxic rats, whereas the isomer beta-lumicolchicine, which does not affect cell microtubular transport, did not inhibit the stimulatory effects of dopamine. The Na,K-ATPase alpha1-subunit protein abundance increased in the basolateral membranes of alveolar type II (ATII) cells incubated with 10(-)5 M DA for 15 min, probably by recruiting Na+ pumps from intracellular pools. Colchicine, but not beta-lumicolchicine, prevented the recruitment of alpha1 subunits to the plasma membrane by DA. Accordingly, DA restored lung ability to clear edema in hyperoxic-injured rat lungs. Conceivably, dopamine induces recruitment of Na+ pumps from intracellular pools to the plasma membrane of alveolar epithelial cells and thus increases lung edema clearance.