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.
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.
Myou
Shigeharu
S
Third Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan. myous@nifty.com
Fujimura
Masaki
M
Kita
Toshiyuki
T
Watanabe
Kazuyoshi
K
Hirose
Tatsuki
T
Tachibana
Hideki
H
Ishiura
Yoshihisa
Y
Nakao
Shinji
S
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*
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