Am. J. Respir. Crit. Care Med., Vol 152, No. 1, 07 1995, 17-23.
The effects of alpha-adrenergic agonists on hyperpnea-induced airway obstruction in dogs
C Omori, W Mitzner and AN Freed
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205, USA.
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.
