The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats.
Circulatory endotoxin can stimulate vagal pulmonary C fibers and rapidly adapting receptors (RARs) in rats, but the underlying mechanisms are not clear. We investigated the involvement of hydroxyl radicals and cyclooxygenase metabolites in the stimulation of C fibers and RARs by circulatory endotoxin (50 mg/kg) in 112 anesthetized, paralyzed, and artificially ventilated rats. In rats pretreated with the vehicle, endotoxin stimulated C fibers and RARs and caused a slight increase in total lung resistance (Rl) and a decrease in dynamic lung compliance. In rats pretreated with dimethylthiourea (a hydroxyl radical scavenger) alone, indomethacin (a cyclooxygenase inhibitor) alone, or a combination of the two, C-fiber and RAR responses [C fiber: change (Delta) = -62, -79, and -85%; RAR: Delta = -80, -84, and -84%, respectively] were reduced, and the Rl response was prevented. The suppressive effects of a combination of dimethylthiourea and indomethacin on the C-fiber and RAR responses were not superior to indomethacin alone. In rats pretreated with isoproterenol (a bronchodilator), the C-fiber response was not significantly affected (Delta = -26%), the RAR response was reduced (Delta = -88%), and the Rl response was prevented. None of these pretreatments affected the dynamic lung compliance response. These results suggest that 1) both hydroxyl radicals and cyclooxygenase metabolites are involved in the endotoxin-induced stimulation of C fibers and RARs, and 2) the involvement of these two metabolites in the C-fiber stimulation may be due to their chemical effects, whereas that in the RAR stimulation may be due to their bronchoconstrictive effects.
Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
Ching Jung
CJ
Lai
Ting
T
Ruan
Yu Ru
YR
Kou
D000200:Action Potentials / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D017665:Hydroxyl Radical / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D004731:Endotoxins; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D011451:Prostaglandin-Endoperoxide Synthases