Hyperventilation-induced airway injury and vascular leakage in dogs: effects of α₁-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.

Airway injury as a mechanism for exercise-induced bronchoconstriction in elite athletes

“…110 It is possible, however, that an increase in MVP might be a normal adaptation to excessive dehydration in an attempt to restore normal ionic and osmotic environment. 80,[116][117][118] Furthermore, an increase in MVP and leakage might be an epiphenomenon of exercise rather than a cause of EIB. 119,120 …”

Contribution ofα- andβ-Adrenergic Mechanisms to the Development of Pulmonary Edema

“…Both PE formation and subsequent death could be prevented with α 1 -adrenergic blockade, while the selective α 2 -adrenoceptor antagonist yohimbine was ineffective [51]. Strong arterial hypertension and increased permeability of pulmonary capillaries due to damage of the capillary walls are crucial pathogenic mechanisms of α 1 -adrenergic stimulation in formation of pulmonary edema [51, 52]. …”