title: Changes in neuroreceptor function of tracheal smooth muscle following acute ozone exposure of guinea pigs.
abstract: We studied the effect of in vivo ozone inhalation (3 ppm, 2 h) on neuroreceptor function in guinea pig tracheal smooth muscle in vitro and the role of the epithelial layer in this process. Changes in smooth muscle tension after stimulation of the muscarinic- and beta-adrenergic receptor were recorded isometrically and stained tracheal tissue sections were histologically evaluated for changes in the epithelial and smooth muscle layer. Ozone exposure resulted in an increase in maximal contraction following stimulation of the muscarinic receptor, whereas pD2 values remained unchanged. After stimulation of the beta-adrenergic receptor no increase in maximal relaxation but only an increase in pD2 value was observed after correction for differences in precontraction level in control- and ozone-exposed situations. Mechanical removal of the epithelial layer resulted in a slight increase of the maximal contraction level after stimulation with methacholine in the control situation, whereas exposure to ozone resulted in a strong decrease of the maximal contraction level under these conditions. Histological stainings showed a slight and focal influx of neutrophilic granulocytes in the epithelial layer, submucosal layer and airway lumen after exposure to ozone. These data support the idea that ozone is able to increase the maximal degree of airway narrowing upon muscarinergic stimulation, i.e. a hyperreactivity response. The results also suggest that functionally altered epithelium plays an important role in the process of ozone-induced hyperreactivity, possibly linked with an early inflammatory response.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: van Hoof
authors.forename: H P
authors.initials: HP
authors.lastname: Voss
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: A J
authors.initials: AJ
authors.lastname: Boere
authors.forename: J A
authors.initials: JA
authors.lastname: Dormans
authors.forename: L
authors.initials: L
authors.lastname: van Bree
authors.forename: A
authors.initials: A
authors.lastname: Bast
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D010083:Oxidants, Photochemical; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010126:Ozone; D007545:Isoproterenol