Isoproterenol improves ability of lung to clear edema in rats exposed to hyperoxia

Exposure of adult rats to 100% O₂ results in lung injury and decreases active sodium transport and lung edema clearance. It has been reported that β-adrenergic agonists increase lung edema clearance in normal rat lungs by upregulating alveolar epithelial Na⁺-K⁺-ATPase function. This study was designed to examine whether isoproterenol (Iso) affects lung edema clearance in rats exposed to 100% O₂ for 64 h. Active Na⁺ transport and lung edema clearance decreased by ~44% in rats exposed to acute hyperoxia. Iso (10^-6 M) increased the ability of the lung to clear edema in room-air-breathing rats (from 0.50 ± 0.02 to 0.99 ± 0.05 ml/h) and in rats exposed to 100% O₂ (from 0.28 ± 0.03 to 0.86 ± 0.09 ml/h; P <0.001). Disruption of intracellular microtubular transport of ion-transporting proteins by colchicine (0.25 mg/100 g body wt) inhibited the stimulatory effects of Iso in hyperoxia-injured rat lungs, whereas the isomer β-lumicolchicine, which does not affect microtubular transport, did not inhibit active Na⁺ transport stimulated by Iso. Accordingly, Iso restored the lung's ability to clear edema after hyperoxic lung injury, probably by stimulation of the recruitment of ion-transporting proteins (Na⁺-K⁺-ATPase) from intracellular pools to the plasma membrane in rat alveolar epithelium.