Hypoxia enhances nonspecific bronchial reactivity

Enhancement of nonspecific bronchial reactivity has been observed after antigen-induced bronchoconstriction, a mast-cell-mediated phenomenon. Because hypoxia also causes degranulation of mast cells, we tested the hypothesis that alveolar hypoxia produces nonspecific bronchial reactivity. In 11 conscious sheep, we determined specific lung resistance (SRL) (mean pulmonary flow resistance times thoracic gas volume) before and after exposure to either air-sham or a hypoxic gas mixture (13% O₂, balance N₂), with and without cromolyn sodium pretreatment. The sheep then received 50 breaths of 5% histamine or 10 breaths of 2.5% carbachol on different days. Inhalation of histamine and carbachol after air-sham caused a significant increase in mean SRL to 350 and 403% of baseline, respectively (p < 0.01). A 30-min exposure to the hypoxic gas mixture, which per se had no effect on SRL, enhanced the histamine and carbachol-induced increases in SRL to 519 and 472% of baseline (p < 0.01). These increases were significantly greater than those observed after air-sham exposure (p < 0.05). Infusion of cromylyn sodium (3 mg/kg/min) before and during exposure to hypoxia prevented the posthypoxia enhancement of histamine-induced (n = 7) and carbachol-induced (n = 5) bronchoconstriction, without affecting the airway responsiveness to these agents during normoxia. These data suggest that alveolar hypoxia enhances nonspecific bronchial reactivity in sheep, which may be related to hypoxia-induced release of mast-cell mediators.