Airway smooth muscle relaxation is impaired in mice lacking the p47 phox subunit of NAD(P)H oxidase

NAD(P)H oxidase is one of the critical enzymes mediating cellular production of reactive oxygen species and has a central role in airway smooth muscle (ASM) cell proliferation. Since reactive oxygen species also affect ASM contractile response, we hypothesized a regulatory role of NAD(P)H oxidase in...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2008-01, Vol.294 (1), p.L139-L148
Main Authors: Chitano, Pasquale, Wang, Lu, Mason, Stanley N., Auten, Richard L., Potts, Erin N., Foster, William M., Sturrock, Anne, Kennedy, Thomas P., Hoidal, John R., Murphy, Thomas M.
Format: Article
Language:English
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Summary:NAD(P)H oxidase is one of the critical enzymes mediating cellular production of reactive oxygen species and has a central role in airway smooth muscle (ASM) cell proliferation. Since reactive oxygen species also affect ASM contractile response, we hypothesized a regulatory role of NAD(P)H oxidase in ASM contractility. We therefore studied ASM function in wild-type mice (C57BL/6J) and mice deficient in a component (p47 phox ) of NAD(P)H oxidase. In histological sections of the trachea, we found that the area occupied by ASM was 17% more in p47 phox−/− than in wild-type mice. After correcting for the difference in ASM content, we found that force generation did not vary between the two genotypes. Similarly, their ASM shortening velocity, maximal power, and sensitivity to acetylcholine, as well as airway responsiveness to methacholine in vivo, were not significantly different. The main finding of this study was a significantly reduced ASM relaxation in p47 phox−/− compared with wild-type mice both during the stimulus and after the end of stimulation. The tension relaxation attained at the 20th second of electric field stimulation was, respectively, 17.6 ± 2.4 and 9.2 ± 2.3% in null and wild-type mice ( P
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00384.2007