Sensory transduction of pulmonary reactive oxygen species by capsaicin-sensitive vagal lung afferent fibres in rats

• Published in: The Journal of physiology Vol. 565; no. 2; pp. 563 - 578
• Main Authors: Ruan, Ting, Shuei Lin, You, Lin, Kae‐Shin, Ru Kou, Yu
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 01-06-2005; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Blood Pressure - drug effects; Capsaicin - pharmacology; Hydrogen Peroxide - pharmacology; Ion Channels - physiology; Lung - innervation; Lung - metabolism; Lung Compliance - drug effects; Male; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Oxidants - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Receptors, Purinergic P2 - physiology; Smoking; Stimulation, Chemical; Tissue, System and Organ Physiology; TRPV Cation Channels; Vagus Nerve - cytology; Vagus Nerve - drug effects; Vagus Nerve - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2005.086181

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 H 2 O 2 (0, 0.2 and 0.4%) produced a concentration-dependant fibre stimulation. The fibre responses to 0.4% H 2 O 2 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 H 2 O 2 ; ΔFA, −96 ± 3%) and were unaffected by the vehicle for dimethylthiourea, iron-saturated deferoxamine or heat-inactivated
catalase. The fibre responses to 0.4% H 2 O 2 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 H 2 O 2 and ·OH, by capsaicin-sensitive vagal lung afferent fibres.