The mechanisms of sensory transduction of pulmonary reactive oxygen species (ROS) by capsaicin-sensitive vagal lung afferent fibres are unclear. To investigate the role of transient receptor potential vanilloid 1 (TRPV1) receptors and P2X purinoceptors in this sensory transduction, we recorded fibre activity (FA) from 132 fibres of this type in 132 anaesthetized and ventilated rats. Airway challenge of aerosolized H2O2 (0, 0.2 and 0.4%) produced a concentration-dependant fibre stimulation. The fibre responses to 0.4% H2O2 were attenuated by dimethylthiourea (a hydroxyl radical (·OH) scavenger; change in fibre activity (ΔFA), -55 ± 9%) or deferoxamine (an iron-chelator that prevents formation of ·OH; ΔFA, -59 ± 9%), were prevented by catalase (an enzyme catalysing H2O2; ΔFA, -96 ± 3%) and were unaffected by the vehicle for dimethylthiourea, iron-saturated deferoxamine or heat-inactivated catalase. The fibre responses to 0.4% H2O2 were attenuated by capsazepine (a TRPV1 receptor antagonist; ΔFA, -39 ± 9%) or iso-pyridoxalphosphate-6-azophenyl-2′,5′-disulphonate (iso-PPADS, a P2X receptor antagonist; ΔFA, -51 ± 9%), were further reduced by capsazepine and iso-PPADS in combination (ΔFA, -70 ± 13%), and were unaltered by their vehicles. The fibre responses to cigarette smoke (20 ml), an irritant that generates ROS, were attenuated by dimethylthiourea (ΔFA, -61 ± 9%) or capsazepine and iso-PPADS in combination (ΔFA, -67 ± 9%). These results suggest that both the TRPV1 and P2X receptors mediate the sensory transduction of ROS, especially H2O2 and ·OH, by capsaicin-sensitive vagal lung afferent fibres.
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