title: Hyperventilation-induced airway injury and vascular leakage in dogs: effects of alpha1-adrenergic agonists.
abstract: alpha1-Adrenergic agonists inhibit hyperventilation-induced bronchoconstriction (HIB) in dogs. We tested the hypothesis that alpha-agonists inhibit HIB by reducing bronchovascular leakage and edema that theoretically could cause airway obstruction. Peripheral airways were isolated by using a bronchoscope; pretreated with either methoxamine (Mx), norepinephrine (NE), or saline aerosol; and then exposed to a 2,000 ml/min dry-air challenge (DAC) for 2 min. Colloidal carbon was injected before DAC and used to quantify bronchovascular permeability. Mx-, NE-, and vehicle-treated airways were prepared for morphometric analysis within 1 h after DAC. Light microscopy revealed that the 2-min DAC produced minimal bronchovascular leakage and little epithelial damage. However, pretreatment with either Mx or NE significantly enhanced dry air-induced bronchovascular hyperpermeability and mucosal injury. The increased damage associated with these alpha1-agonists implicates a protective role for the bronchial circulation. The fact that alpha1-agonists inhibit HIB suggests that neither dry air-induced leakage nor injury directly contributes to the development of airway obstruction. In addition, our data suggest that alpha-agonists attenuate HIB in part by augmenting hyperventilation-induced bronchovascular leakage and by replacing airway water lost during a DAC.
authors.affiliation: Department of Environmental Health Sciences, Division of Physiology, The Johns Hopkins University, Baltimore, Maryland 21205, USA. afreed@jhsph.edu
authors.forename: A N
authors.initials: AN
authors.lastname: Freed
authors.forename: V
authors.initials: V
authors.lastname: Taskar
authors.forename: B
authors.initials: B
authors.lastname: Schofield
authors.forename: C
authors.initials: C
authors.lastname: Omori
mesh_terms: D000280:Administration, Inhalation; D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000336:Aerosols; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D019559:Capillary Leak Syndrome / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D006985:Hyperventilation / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000503:physiopathology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000336:Aerosols; D009638:Norepinephrine