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

Spontaneous inhalation of wood smoke (~ 6 ml) 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.