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.
Omori
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Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Mitzner
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Freed
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D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000098:blood supply*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D006813:Humidity; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D000336:Aerosols; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008729:Methoxamine; D000109:Acetylcholine; D009638:Norepinephrine