Inhibitory effect of gas phase cigarette smoke on breathing: role of hydroxyl radical

Abstract

Inhaling cigarette smokes evokes immediate bradypnea in rats, resulting from stimulation of vagal bronchopulmonary C-fiber afferents by smoke constituent(s) other than nicotine. To determine the contribution of the gas phase of smoke to this irritant effect, the acute respiratory responses to both cigarette smoke and gas phase smoke were studied and compared in anesthetized Sprague-Dawley rats; smoke (6 ml, 50%) was generated by a machine from low-nicotine research cigarettes and the gas phase was obtained by passing the smoke through a glass-fiber Cambridge filter. Inhalation of gas phase smoke alone evoked a transient inhibitory effect on breathing, prolonging expiratory time (Te) to peak of 159 ± 6% of the base line; this response was very similar to that triggered by inhaling the unified smoke (Te = 177 ± 12%). The bradypnea started within 1–4 breaths after the onset of smoke inhalation, lasted for 3–5 breaths and was completely abolished by vagotomy. This inhibitory effect of gas phase smoke on breathing was also largely prevented after a pretreatment with either intravenous infusion or aerosol inhalation of hydroxyl radical scavenger, dimethylthiourea. These results suggest that the gas phase is primarily responsible for eliciting the reflexogenic bradypneic response to cigarette smoke in anesthetized rats and that hydroxyl radicals released endogenously in the lungs may be involved.