title: Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma.
abstract: It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma. Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a double-blind, randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)-PEF(40) values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.
authors.affiliation: Third Department of Internal Medicine and Department of Laboratory Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. myous@p2222.nsk.ne.jp
authors.forename: S
authors.initials: S
authors.lastname: Myou
authors.forename: M
authors.initials: M
authors.lastname: Fujimura
authors.forename: Y
authors.initials: Y
authors.lastname: Kamio
authors.forename: Y
authors.initials: Y
authors.lastname: Ishiura
authors.forename: K
authors.initials: K
authors.lastname: Kurashima
authors.forename: H
authors.initials: H
authors.lastname: Tachibana
authors.forename: T
authors.initials: T
authors.lastname: Hirose
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D016210:Methacholine Chloride; D019808:Losartan