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Nadph oxidase regulates alveolar epithelial sodium channel (ENaC) activity and lung fluid balance in vivo via O 2 ‐ signaling
Author(s) -
Helms My N,
Goodson Preston,
Jain Lucky,
Koval Michael
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.696.4
Subject(s) - epithelial sodium channel , nadph oxidase , in vivo , lung , chemistry , reactive oxygen species , stimulation , medicine , endocrinology , sodium , biology , biochemistry , microbiology and biotechnology , organic chemistry
To define roles for reactive oxygen species (ROS) and ENaC in maintaining lung fluid balance in vivo , we used multispectral and X‐ray imaging of C57BL/6J mouse lungs. We found that inhibition of NADPH oxidase with a Rac‐1 inhibitor, NSC23766 , resulted in alveolar flooding which correlated with a decrease in lung ROS production in vivo . Consistent with a role for Nox2 in alveolar fluid balance, Nox2 −/− mice showed increased retention of airspace fluid as compared to wild type controls. Interestingly, X‐ray analysis of C57BL/6J lungs IT instilled with LPS showed an acute stimulation of lung fluid clearance and ROS production in vivo which was abrogated by the ROS scavenger tetramethylpiperidine‐N‐oxyl (TEMPO). Acute application of LPS increased the activity of 20pS non‐selective ENaC channels by individual rat type 1 cells; the average number of channel and single channel open probability (NPo) increased from 0.14 ± 0.04 to 0.62 ± 0.23. Application of TEMPO to the same cell attached recording caused an immediate significant decrease in ENaC NPo to 0.04 ± 0.03. These data demonstrate that, in vivo , ROS has the capacity to stimulate lung fluid clearance by increasing ENaC activity. NIH R00‐HL‐09222601awarded to MH.