TY - JOUR
T1 - Hypoxia-induced enhancement of nonspecific bronchial reactivity
T2 - Role of leukotrienes
AU - D'Brot, J.
AU - Ahmed, T.
PY - 1988
Y1 - 1988
N2 - Because alveolar hypoxia has been shown to cause an increase of leukotrienes in lung lavage fluid, we tested the hypothesis that enhancement of nonspecific bronchial reactivity during alveolar hypoxia may be mediated by leukotrienes. In nine conscious sheep we determined specific lung resistance (sRL) before and after exposure to either air or a hypoxic gas mixture (13% O2) for 30 min. The sheep then inhaled 50 breaths of aerosolized 5% histamin solution (n=6) or 10 breaths of 2.5% carbachol solution (n = 6) on different days, and the measurements of sRL were repeated. On subsequent days the above protocols were repeated after pretreatment with aerosolized FPL 57231 (3 ml, 1% solution), a leukotriene receptor antagonist. Inhalation of histamine and carbachol after exposure to air caused an increase in mean sRL to 337 and 342% of base line, respectively (P < 0.05). Exposure to the hypoxic gas mixture had no effect on sRL but enhanced the histamine- and carbachol-induced increase in mean sRL to 621 and 646% of base line, respectively (P < 0.05); these increases were significantly higher than those observed after air exposure (P < 0.05). FPL 57231 prevented the hypoxia-induced enhancement of bronchial reactivity to histamine and carbachol without affecting the airway responsiveness to these agents after air. In another group of eight sheep, aerosolized leukotriene C4, at a dose (50 μg) that per se had no effect on sRL, enhanced the bronchial reactivity to carbachol. These data suggest that in sheep during alveolar hypoxia airway hyperresponsiveness may be due to the priming of airway smooth muscle by leukotrienes.
AB - Because alveolar hypoxia has been shown to cause an increase of leukotrienes in lung lavage fluid, we tested the hypothesis that enhancement of nonspecific bronchial reactivity during alveolar hypoxia may be mediated by leukotrienes. In nine conscious sheep we determined specific lung resistance (sRL) before and after exposure to either air or a hypoxic gas mixture (13% O2) for 30 min. The sheep then inhaled 50 breaths of aerosolized 5% histamin solution (n=6) or 10 breaths of 2.5% carbachol solution (n = 6) on different days, and the measurements of sRL were repeated. On subsequent days the above protocols were repeated after pretreatment with aerosolized FPL 57231 (3 ml, 1% solution), a leukotriene receptor antagonist. Inhalation of histamine and carbachol after exposure to air caused an increase in mean sRL to 337 and 342% of base line, respectively (P < 0.05). Exposure to the hypoxic gas mixture had no effect on sRL but enhanced the histamine- and carbachol-induced increase in mean sRL to 621 and 646% of base line, respectively (P < 0.05); these increases were significantly higher than those observed after air exposure (P < 0.05). FPL 57231 prevented the hypoxia-induced enhancement of bronchial reactivity to histamine and carbachol without affecting the airway responsiveness to these agents after air. In another group of eight sheep, aerosolized leukotriene C4, at a dose (50 μg) that per se had no effect on sRL, enhanced the bronchial reactivity to carbachol. These data suggest that in sheep during alveolar hypoxia airway hyperresponsiveness may be due to the priming of airway smooth muscle by leukotrienes.
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U2 - 10.1152/jappl.1988.65.1.194
DO - 10.1152/jappl.1988.65.1.194
M3 - Article
C2 - 3403464
AN - SCOPUS:0023687641
VL - 65
SP - 194
EP - 199
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 1
ER -