Intermittent hypoxia enhances chemical sensitivity of pulmonary C fibers in rats: role of reactive oxygen species

Abstract

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH) during sleep. Clinically, OSA may occur concomitantly with noturnal asthma and cough reflex, it is likely that involves hypersensitivity of pulmonary C fibers (PCFs) during airway inflammation. This study was performed to determine whether the excitabilities of PCFs to chemical and mechanical stimuli are altered by IH‐induced production of reactive oxygen species (ROS). In anesthetized, open‐chest, and artificially ventilated rats, delivered ten episodes (30 s of N2 + 30 s of 21% O2) of IH into the lungs significantly enhanced phrenic apnea to intravenous injection of capsaicin, a selective stimulant of PCFs. Bilateral vagotomy abolished apneic response to capsaicin both before and after IH. Subsequent recording of single‐fiber activity of PCFs (PCFA) showed that IH caused a slight increase in baseline PCFA. Additionally, IH markedly enhanced PCFA to capsaicin injection, and this enhanced response lasted for more than 30 min after termination of IH. In contrast, IH did not change the response of PCFA to lung inflation. The potentiating responses of these PCFs to capsaicin after IH were greatly attenuated by pretreatment with dimethylthiourea, a hydroxyl radical scavenger. These results suggest that IH augments the responses of the C‐fiber afferents to capsaicin, and this potentiating effect of IH is mediated through the action of ROS.