Eicosanoids modulate hyperpnea-induced late phase airway obstruction and hyperreactivity in dogs.
A canine model of exercise-induced asthma was used to test the hypothesis that the development of a late phase response to hyperventilation depends on the acute production of pro-inflammatory mediators. Peripheral airway resistance, reactivity to hypocapnia and aerosol histamine, and bronchoalveolar lavage fluid (BALF) cell and eicosanoid content were measured in dogs approximately 5 h after dry air challenge (DAC). DAC resulted in late phase obstruction, hyperreactivity to histamine, and neutrophilic inflammation. Both cyclooxygenase and lipoxygenase inhibitors administered in separate experiments attenuated the late phase airway obstruction and hyperreactivity to histamine. Neither drug affected the late phase inflammation nor the concentrations of eicosanoids in the BALF obtained 5 h after DAC. This study confirms that hyperventilation of peripheral airways with unconditioned air causes late phase neutrophilia, airway obstruction, and hyperreactivity. The late phase changes in airway mechanics are related to the hyperventilation-induced release of both prostaglandins and leukotrienes, and appear to be independent of the late phase infiltration of inflammatory cells.
Davis
Michael S
MS
Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins Medical Institutions, 615 North Wolfe Street, Baltimore, MD 21205, USA. msdavis@okstate.edu
McCulloch
Sharron
S
Myers
Teresa
T
Freed
Arthur N
AN
D000388:Air; D000402:Airway Obstruction / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004285:Dogs; D015777:Eicosanoids / Q000032:analysis / Q000502:physiology*; D006813:Humidity; D006985:Hyperventilation / Q000150:complications*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D012119:Respiration
D015777:Eicosanoids; D016291:Dizocilpine Maleate; D007213:Indomethacin