Dopamine increases lung liquid clearance during mechanical ventilation

Short-term mechanical ventilation with high tidal volume (HVT) causes mild to moderate lung injury and impairs active Na+ transport and lung liquid clearance in rats. Dopamine (DA) enhances active Na+ transport in normal rat lungs by increasing Na+ -K+ ATPase activity in the alveolar epithelium. We examined whether DA would increase alveolar fluid reabsorption in rats ventilated with HVT for 40 min compared with those ventilated with low tidal volume (LVT) and with nonventilated rats. Similar to previous reports, HVT ventilation decreased alveolar fluid reabsorption by similar to50% (P < 0.001). DA increased alveolar fluid reabsorption in nonventilated control rats (by similar to 60%), LVT ventilated rats (by similar to 55%), and HVT ventilated rats (by similar to 200%). In parallel studies, DA increased Na+-K+-ATPase activity in cultured rat alveolar epithelial type II cells (ATII). Depolymerization of cellular microtubules by colchicine inhibited the effect of DA on HVT ventilated rats as well as on Na+-K+-ATPase activity in ATII cells. Neither DA nor colchicine affected the short-term Na+ K K+-ATPase alpha(1)- and beta(1)-subunit mRNA steady-state levels or total alpha(1)- and beta(1)-subunit protein abundance in ATII cells. Thus we reason that DA improved alveolar fluid reabsorption in rats ventilated with HVT by upregulating the Na+-K+ ATPase function in alveolar epithelial cells.