Dexmedetomidine enhances human lung fluid clearance through improving alveolar sodium transport

Accumulating evidence shows that dexmedetomidine can attenuate lung edema with acute lung injury in experimental mouse and rat models, but the mechanisms of dexmedetomidine on human alveolar fluid transport are still unknown. We measured the effects of dexmedetomidine on alveolar fluid clearance in human lung lobes ex vivo. Moreover, we measured the regulation of transepithelial Na⁺ transport by dexmedetomidine in H441 cells by electrophysiological technique and Western blot method. Our results showed that intratracheal instillation of dexmedetomidine markedly increased the reabsorption of 5% bovine serum albumin instillate (19.8 ± 1.4%, P < 0.01 vs. Control, n = 5). Further studies suggested that dexmedetomidine increased amiloride-sensitive short-circuit currents in permeabilized H441 monolayers and whole cell amiloride-sensitive Na⁺ currents in a dose-dependent fashion. Real-time PCR and Western blot results showed that dexmedetomidine could enhance the mRNA and protein expression of α-ENaC subunit, while inhibiting the phosphorylation of ERK_1/2 . These data demonstrate that dexmedetomidine could improve human lung fluid clearance and lung epithelial Na⁺ channel activity, and these effects may be mediated through the enhancement of α-ENaC expression and inhibition of ERK_1/2 pathway.