Miller, Andrew D

Background Fluid flux in the lungs is influenced by factors altering accumulation or removal (e.g., stimulation of epithelium sodium channels, ENaC). Purpose To determine if ENaC are necessary in the normal fluid regulation with simulated altitude exposure. Methods/Results On separate occasions, 19 healthy subjects (27 ± 5 y) received either nebulized amiloride (ENaC antagonist) or placebo (nebulized saline) during 17 h normobaric hypoxia (FIO2 = 12.5%) in a randomized, double‐blind fashion. Lung diffusing capacity for carbon monoxide (DLCO), alveolar‐capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) were measured via a rebreathe method before and after hypoxic exposure. DLCO was not different at baseline for the amiloride vs. placebo treatments (19 ± 5 vs. 21 ± 8 mL/min/mmHg). Hypoxic exposure increased Vc but did not change Dm in both treatments (Placebo: Vc = 43 ± 22 vs. 59±23 mL p=0.011, Dm = 35 ± 10 vs. 37 ± 12 mL/min/mmHg p=0.312; Amiloride: Vc = 38 ± 17 vs. 57 ± 22 mL p<0.01, Dm = 31 ± 8 vs. 34 ± 10 mL/min/mmHg p= 0.206). Conclusion Normobaric hypoxia did not differentially affect alveolar‐capillary conductance in amiloride and placebo conditions, suggesting that ENaC do not have a role in normal lung fluid regulation during acute hypoxic exposure. HL71478