title: Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.
abstract: BACKGROUND
  Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known.
  
  
  OBJECTIVE
  To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs.
  
  
  METHODS
  Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge.
  
  
  RESULTS
  Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge.
  
  
  CONCLUSIONS
  Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.
authors.affiliation: Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. myous@nifty.com
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Hirose
authors.forename: Hideki
authors.initials: H
authors.lastname: Tachibana
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ishiura
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D011725:Pyridines / Q000627:therapeutic use; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000941:Antigens; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C073402:PD 123319; C081643:candesartan