Role of smooth muscle alpha 1-receptors in nonspecific bronchial responsiveness in asthma.
It has been postulated that the wide range of bronchial hyperresponsiveness to nonspecific stimuli, such as methacholine, found in asthmatics could be due to increased alpha-adrenergic receptor activity in the airways. We examined alpha 1- receptor responsiveness by comparing the responses obtained after inhaling the alpha 1-agonist phenylephrine (2 to 32 mg/ml) with the responses obtained after inhaling buffered saline in 10 asthmatics in whom the provocation concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) ranged from 0.13 to 9.19 mg/ml. Subjects were pretreated with inhaled atropine (3 mg nebulized during tidal breathing) and inhaled propranolol (3 mg nebulized during tidal breathing) to exclude cholinergic and beta receptor activity influencing bronchial smooth muscle responsiveness. After pretreatment drugs, the mean value for FEV1 before phenylephrine inhalations did not differ significantly from that before the control inhalations of saline. There was no significant change in FEV1 after phenylephrine compared with that after saline, suggesting that bronchial smooth muscle alpha 1-adrenergic receptor activity was not present. We conclude that increased bronchial smooth muscle alpha 1-receptor activity is not the primary abnormality producing the variability between asthmatics in nonspecific bronchial hyperresponsiveness.
D000328:Adult; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D001285:Atropine / Q000627:therapeutic use; D001980:Bronchi / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008688:Methacholine Compounds; D008875:Middle Aged; D009130:Muscle, Smooth / Q000503:physiopathology*; D010656:Phenylephrine; D011292:Premedication; D011433:Propranolol / Q000627:therapeutic use; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride; D014797:Vital Capacity
D008688:Methacholine Compounds; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D012965:Sodium Chloride; D001285:Atropine; D011433:Propranolol