title: Nasal hyperresponsiveness to histamine induced by repetitive exposure to cedar pollen in guinea-pigs.
abstract: Nasal hyperresponsiveness is one of the characteristic features of the pathogenesis of allergic rhinitis. This study examined whether repetitive inhalation of antigen (Japanese cedar pollen) led to the development of nasal hyperresponsiveness to histamine in sensitized conscious guinea-pigs. Guinea-pigs were repeatedly challenged by pollen inhalation once every week following sensitization by means of intranasal application of pollen extract plus aluminium hydroxide. The upper airways obstruction (increase in specific airway resistance (sRaw)) in response to intranasally instilled histamine was measured as an index of nasal (hyper)responsiveness. The hyperresponsiveness to histamine gradually developed with repeated pollen inhalation challenge, and the airway response at the 20th and 24th challenges was three to four orders of magnitude higher than that in nonsensitized animals. Similar degrees of hyperresponsiveness were observed at 10 h and 2 days after a pollen inhalation challenge, but the hyperresponsiveness had almost disappeared by day 7. The increased responsiveness was suppressed by pretreatment with mepyramine but not with atropine. The maximum sRaw, which was observed 10 min after histamine instillation, was largely blocked by naphazoline. Hyperresponsiveness was hardly observed on methacholine instillation. The present allergic rhinitis model, showing marked nasal hyperresponsiveness to histamine after repeated intranasal allergen challenge in guinea pigs, should be useful for investigating the pathogenesis of allergic rhinitis.
authors.affiliation: Dept of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mizutani
authors.forename: T
authors.initials: T
authors.lastname: Nabe
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Takenaka
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine; D007114:Immunization; D008297:Male; D016210:Methacholine Chloride; D009278:Naphazoline / Q000494:pharmacology; D009296:Nasal Cavity / Q000187:drug effects / Q000276:immunology; D011058:Pollen / Q000009:adverse effects*; D011738:Pyrilamine / Q000494:pharmacology; D012016:Reference Values; D012130:Respiratory Hypersensitivity / Q000175:diagnosis / Q000209:etiology*; D012221:Rhinitis, Allergic, Perennial / Q000175:diagnosis* / Q000209:etiology*; D012680:Sensitivity and Specificity; D014197:Trees
chemical_list: D000485:Allergens; D016210:Methacholine Chloride; D001285:Atropine; D006632:Histamine; D009278:Naphazoline; D011738:Pyrilamine