THE EFFECTS OF ALPHA-ADRENERGIC AGONISTS ON HYPERPNEA-INDUCED AIRWAY-OBSTRUCTION IN DOGS

Two alpha-adrenergic agonists that inhibit hyperpnea-induced airway ob struction (HIAO) in asthmatic subjects were used to examine the role o f bronchial blood flow in the development of HIAO in canine periphery airways. A bronchoscope was used to record peripheral airway resistanc e (R(p)) in anesthetized dogs before and after hyperpnea with dry air. Hyperpnea increased R(p) 64 +/- 8% (mean +/- SE) above baseline. Trea tment with norepinephrine (NOR) either before or at various times afte r hyperpnea inhibited HIAO (p < 0.01). We also found that NOR inhibite d acetylcholine-induced bronchoconstriction. However, beta-adrenergic blockade with propranolol completely eliminated these effects. Thus, N OR 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) decreas ed HIAO by similar to 25% when compared with the vehicle control, and this effect was completely eliminated by alpha-adrenergic blockade wit h phentolamine. Relative to NOR, MX provides weak protection against H IAO via the direct stimulation of a-adrenergic receptors and their sub sequent effect on either mucus secretion or bronchovascular tone. We c onclude that bronchial blood flow plays at best a minor role in the de velopment of HIAO.