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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/L139    most recent 00384.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Chitano, P. Articles by Murphy, T. M. Search for Related Content PubMed PubMed Citation Articles by Chitano, P. Articles by Murphy, T. M.

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

Departments of ¹Pediatrics and Neonatal Perinatal Research Institute and ²Medicine, Duke University Medical Center, Durham, North Carolina; and ³Department of Internal Medicine, University of Utah, Salt Lake City, Utah

Submitted 13 September 2007 ; accepted in final form 7 November 2007

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 <0.01 by t-test). Similar significant differences were found in the rate of tension relaxation and the time required to reduce tension by one-half. Our data suggest that NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue. Most importantly, we report the first evidence that the p47^phox subunit of NAD(P)H oxidase plays a role in ASM relaxation.

airways; airway responsiveness; contractility; reactive oxygen species