title: Arachidonic acid products in airway nociceptor activation during acute lung injury.
abstract: We have reported that airway nociceptors [C fibre receptors (CFRs) and high-threshold Aδ fibre receptors (HTARs)] are activated during oleic acid (OA)-induced acute lung injury. In the present studies, we tested the hypothesis that this nociceptor activation is mediated by arachidonic acid products. In anaesthetized, open-chest, mechanically ventilated rabbits, we examined the response of the nociceptors to intravenous injection of OA before and after blocking the cyclo-oxygenase pathways with indomethacin. Pretreatment with indomethacin (20 mg kg(-1)) decreased the background activities of both CFRs (from 0.48 ± 0.12 to 0.25 ± 0.08 impulses/s, n = 7, P < 0.05) and HTARs (from 0.54 ± 0.14 to 0.23 ± 0.08 impulses/s, n = 10, P < 0.01). It also blocked the response of the nociceptors to OA. Likewise, pretreatment with thromboxane synthase inhibitor (ketoconazole) also blocked the nociceptor response to OA. In addition, local microinjection or intravenous injection of a thromboxane mimetic stimulated CFRs and HTARs. The present results clearly indicate that arachidonic acid metabolites mediate airway nociceptor activation during OA-induced acute lung injury and suggest that thromboxane may be a key mediator.
authors.affiliation: Department of Medicine, University of Louisville, 550 South Jackson Street, Louisville, KY 40292, USA.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Lin
authors.forename: Huafeng
authors.initials: H
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Bogdan
authors.initials: B
authors.lastname: Moldoveanu
authors.forename: Juan
authors.initials: J
authors.lastname: Guardiola
authors.forename: Jerry
authors.initials: J
authors.lastname: Yu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D019301:Oleic Acid; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D016718:Arachidonic Acid; D019301:Oleic Acid; D013930:Thromboxane-A Synthase; D007654:Ketoconazole; D007213:Indomethacin