Involvement of hydroxyl radical in the immediate ventilatory responses to inhaled wood smoke in rats

Spontaneous inhalation of wood smoke (similar to 6 mi) via a tracheostomy immediately triggered either a slowing of respiration (SR, n = 51) or an augmented inspiration (AI, n = 32) in 83 anesthetized Sprague-Dawley rats studied. To investigate the involvement of hydroxyl radical (OH.) in evoking these immediate smoke-induced ventilatory responses, smoke challenges were repeated following intravenous infusion (0.05 ml/min for 20 min) of saline vehicle, dimethylthiourea (DMTU, 500 mg/kg), deferoxamine (DEF, 20 mg/kg), or iron-saturated DEF (DEF+Fe, 20 mg/kg). DMTU is a scavenger for OH.. DEF is an iron-chelator which prevents the formation of OH., whereas DEF saturated with iron results in the loss of its iron-chelating properties. In the vehicle group, both the SR (n = 8) and the AI (n = 7) were unaffected by the pretreatment. However, in the DMTU group, the SR (n = 23) was abolished in seven and attenuated in 16 rats, while the AI (n = 10) was eliminated in eight and unaffected in two rats. In the DEF group, the SR (n = 12) was abolished in three and attenuated in nine rats, while the AI (n = 8) was eliminated in six and unaffected in two rats. In contrast, in the DEF + Fe group, both the SR (n = 8) and the AI (n = 7) were not attenuated by the pretreatment. These results suggest that an increase in OH. burden following smoke inhalation is actively involved in evoking the acute irritant effects of wood smoke on breathing in rats. (C) 1997 Elsevier Science B.V.