Eicosanoid and muscarinic receptor blockade abolishes hyperventilation-induced bronchoconstriction.
This study was designed to test the hypothesis that hyperventilation-induced bronchoconstriction (HIB) results from the combined effects of prostanoid and leukotriene metabolism. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance and HIB before and after combined treatment with inhibitors of cyclooxygenase (indomethacin) and 5-lipoxygenase (MK-0591). Bronchoalveolar lavage fluid (BALF) cells and mediators from hyperventilated and control airways were also measured. Pretreatment with MK-0591 and indomethacin significantly attenuated, but did not abolish, HIB. However, addition of atropine nearly eliminated the residual response. Blockade of eicosanoid metabolism markedly reduced the concentrations of eicosanoids recovered in BALF after hyperventilation. Positive correlations between posthyperventilation BALF prostanoid and epithelial cell concentrations are suggestive of mucosal injury-induced mediator production and release. We conclude that HIB is prevented in the presence of eicosanoid and muscarinic-receptor blockade and that both classes of eicosanoids contribute similarly to the development of HIB.
Freed
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Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
McCulloch
S
S
Wang
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Y
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000032:analysis; D004285:Dogs; D015777:Eicosanoids / Q000037:antagonists & inhibitors*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006985:Hyperventilation / Q000188:drug therapy* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000032:analysis; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013928:Thromboxane A2 / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D015289:Leukotrienes; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D013928:Thromboxane A2; D015237:Dinoprost; D001094:Arachidonate 5-Lipoxygenase; D007213:Indomethacin