Hyperventilation-induced airway injury and vascular leakage in dogs: effects of alpha 1-adrenergic agonists

Freed, Arthur N., Varsha Taskar, Brian Schofield, andChiharu Omori. Hyperventilation-induced airway injury and vascular leakage in dogs: effects of₁-adrenergic agonists.J. Appl. Physiol. 83(6):1884-1889, 1997.₁-Adrenergic agonistsinhibit hyperventilation-induced bronchoconstriction (HIB) in dogs. Wetested the hypothesis that -agonists inhibit HIB byreducing bronchovascular leakage and edema that theoretically couldcause airway obstruction. Peripheral airways were isolated by using abronchoscope; pretreated with either methoxamine (Mx), norepinephrine(NE), or saline aerosol; and then exposed to a 2,000 ml/min dry-airchallenge (DAC) for 2 min. Colloidal carbon was injected before DAC andused to quantify bronchovascular permeability. Mx-, NE-, andvehicle-treated airways were prepared for morphometric analysis within1 h after DAC. Light microscopy revealed that the 2-min DAC producedminimal bronchovascular leakage and little epithelial damage. However, pretreatment with either Mx or NE significantly enhanced dryair-induced bronchovascular hyperpermeability and mucosal injury. Theincreased damage associated with these₁-agonists implicates aprotective role for the bronchial circulation. The factthat ₁-agonists inhibit HIBsuggests that neither dry air-induced leakage nor injury directlycontributes to the development of airway obstruction. In addition,our data suggest that-agonists attenuate HIB in part byaugmenting hyperventilation-induced bronchovascular leakage and byreplacing airway water lost during a DAC.