Low-dose carbon monoxide reduces airway hyperresponsiveness in mice. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bronchoconstriction
  • Cyclic GMP
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Muscle, Smooth
  • Pneumonia

MeSH Major

  • Airway Resistance
  • Bronchial Hyperreactivity
  • Carbon Monoxide

abstract

  • Carbon monoxide (CO) in expired gas has been shown to be elevated with asthma; however, its function is not known, and there is some potential that it may serve a bronchoprotective role to decrease airway hyperresponsiveness (AHR). Thus the ability of CO to reverse methacholine (MCh)-induced bronchoconstriction was evaluated in C57BL/6 (C57) and A/J mice with and without airway inflammation produced by ovalbumin (OVA). Acutely administered CO (1% in air, 10 min) reduced MCh-driven increases in lung resistance in OVA-challenged C57 mice by an average of 50% (from 14.5 to 7.1 cmH2O.ml-1.s-1), whereas no effect was observed in naïve C57 mice or OVA-challenged C57 mice inhaling air alone. Acutely inhaled CO (500 ppm = 0.05%, for 10 min) reduced MCh-induced airway reactivity (AR) by 20-60% in airway hyperresponsive naïve A/J mice, whereas repeated 10-min administrations of 500 ppm CO over a 5-day period decreased AR by 50%. Repeated administration of low-dose CO [250 (0.025%) and (0.05%) 500 ppm, 1 h/day, 5 days] to A/J mice with airway inflammation likewise resulted in a drop of AR by 50%, compared with those not receiving CO. Inhibition of guanylyl cyclase/guanosine 3',5'-cyclic monophosphothioate (cGMP) using 1H-[1,2,4] oxydiazolo[4,3-a]quinoxalin-1-one or a competitive inhibitor, Rp diastereomers of 8-bromo-cGMP, resulted in inhibition of the effect of CO on AHR, suggesting that the effects of CO were mediated through this mechanism. These results indicate that low-dose CO can effectively reverse AHR in the presence and absence of airway inflammation in mice and suggest a potential role for CO in the modulation of AHR.

publication date

  • December 2003

has subject area

  • Airway Resistance
  • Animals
  • Bronchial Hyperreactivity
  • Bronchoconstriction
  • Carbon Monoxide
  • Cyclic GMP
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Muscle, Smooth
  • Pneumonia

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00145.2003

PubMed ID

  • 12896878

Additional Document Info

start page

  • L1270

end page

  • L1276

volume

  • 285

number

  • 6