HYPERVENTILATION-INDUCED AIRWAY INJURY AND VASCULAR LEAKAGE IN DOGS -EFFECTS OF ALPHA(1)-ADRENERGIC AGONISTS

alpha(1)-Adrenergic agonists inhibit hyperventilation-induced bronchoc onstriction (HIB) in dogs. We tested the hypothesis that ol-agonists i nhibit HIB by reducing bronchovascular leakage and edema that theoreti cally could cause airway obstruction. Peripheral airways were isolated by using a bronchoscope; pretreated with either methoxamine (Mx), nor epinephrine (NE), or saline aerosol; and then exposed to a 2,000 ml/mi n dry-air challenge (DAC) for 2 min. Colloidal carbon was injected bef ore DAC and used to quantify bronchovascular permeability. Mx-, NE-, a nd vehicle-treated airways were prepared for morphometric analysis wit hin 1 h after DAC. Light microscopy revealed that the 2-min DAC produc ed minimal bronchovascular leakage and little epithelial damage. Howev er, pretreatment with either Mx or NE significantly enhanced dry air-i nduced bronchovascular hyperpermeability and mucosal injury. The incre ased damage associated with these alpha(1)-agonists implicates a prote ctive role for the bronchial circulation. The fact that al-agonists in hibit HIB suggests that neither dry air-induced leakage nor injury dir ectly contributes to the development of airway obstruction. In additio n, our data suggest that ol-agonists attenuate HIB in part by augmenti ng hyperventilation-induced bronchovascular leakage and by replacing a irway water lost during a DAC.