Dopamine Restores Lung Ability to Clear Edema in Rats Exposed to Hyperoxia

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Abstract
Exposure to hyperoxia causes lung injury, decreases active sodium transport and lung edema clear- ance in rats. Dopamine (DA) increases lung edema clearance by stimulating vectorial Na 1 flux and Na,K-ATPase function in rat alveolar epithelium. This study was designed to test whether DA (10 2 5 M) would increase lung edema clearance in rats exposed to 100% O 2 for 64 h. Active Na 1 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 6 0.02 to 0.75 6 0.06 ml/h) and in rats exposed to 100% O 2 (from 0.28 6 0.03 to 0.67 6 0.03 ml/h). Disruption of cell microtubular transport system by colchicine blocked the stimulatory effect of DA on active Na 1 trans- port in control and hyperoxic rats, whereas the isomer b -lumicolchicine, which does not affect cell microtubular transport, did not inhibit the stimulatory effects of dopamine. The Na,K-ATPase a 1 -sub- unit protein abundance increased in the basolateral membranes of alveolar type II (ATII) cells incu- bated with 10 2 5 M DA for 15 min, probably by recruiting Na 1 pumps from intracellular pools. Colchi- cine, but not b -lumicolchicine, prevented the recruitment of a 1 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 1 pumps from intracellular pools to the plasma membrane of al- veolar epithelial cells and thus increases lung edema clearance. Saldías FJ, Lecuona E, Comellas AP, Ridge KM, Sznajder JI. Dopamine restores lung ability to clear edema in rats exposed to hy- peroxia. AM J RESPIR CRIT CARE MED 1999;159:626-633.