The effects of alpha-adrenergic agonists on hyperpnea-induced airway obstruction in dogs

Two alpha-adrenergic agonists that inhibit hyperpnea-induced airway obstruction (HIAO) in asthmatic subjects were used to examine the role of bronchial blood flow in the development of HIAO in canine periphery airways. A bronchoscope was used to record peripheral airway resistance (Rp) in anesthetized dogs before and after hyperpnea with dry air. Hyperpnea increased Rp 64 +/- 8% (mean +/- SE) above baseline. Treatment with norepinephrine (NOR) either before or at various times after hyperpnea inhibited HIAO (p < 0.01). We also found that NOR inhibited acetylcholine-induced bronchoconstriction. However, beta-adrenergic blockade with propranolol completely eliminated these effects. Thus, NOR inhibited HIAO in canine peripheral airways via the stimulation of beta-adrenergic receptors and the attenuation of airway smooth muscle contractility. In contrast, pretreatment with methoxamine (MX) decreased HIAO by approximately 25% when compared with the vehicle control, and this effect was completely eliminated by alpha-adrenergic blockade with phentolamine. Relative to NOR, MX provides weak protection against HIAO via the direct stimulation of alpha-adrenergic receptors and their subsequent effect on either mucus secretion or bronchovascular tone. We conclude that bronchial blood flow plays at best a minor role in the development of HIAO.