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J Appl Physiol (October 1, 2004). doi:10.1152/japplphysiol.00539.2004
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Submitted on May 21, 2004
Accepted on September 28, 2004

The Involvement of Hydroxyl Radical and Cyclooxygenase Metabolites in the Activation of Lung Vagal Sensory Receptors by Circulatory Endotoxin in Rats

Ching Jung Lai1, Ting Ruan2, and Yu Ru Kou2*

1 Deptartment of Physiology, Tzu Chi University, Hualien, Taiwan
2 Institute of Physiology, National Yang-Ming University, School of Medicine, Taipei, Taiwan

* To whom correspondence should be addressed. E-mail: yrkou{at}ym.edu.tw.

Circulatory endotoxin can stimulate vagal pulmonary C fibers (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-1) 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 (Cdyn). 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: {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 Cdyn response. These results suggest that 1) both hydroxyl radicals and cyclooxygenase metabolites are involved in the endotoxin-induced stimulation of C-fiber 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.




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