Antigen-induced airway responses are inhibited by a potassium channel opener.
We have investigated the effect of a potassium channel opener, BRL 38227, on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs by simultaneously measuring pulmonary resistance (Rl) and extravasation of Evans blue dye. Guinea pigs were sensitized 3 wk before experimentation with ovalbumin (OA) and aluminum hydroxide. The trachea was cannulated, and lungs were mechanically ventilated. All animals were pretreated 30 min before experimentation with atropine (1 mg/kg intravenously) and propranolol 1 mg/kg to block muscarinic and beta-adrenergic responses, respectively. BRL 38227 (200 micrograms/kg) was administered intravenously 1 min before intravenous dye injection (30 mg/kg); OA (3 mg/ml) was inhaled using an ultrasonic nebulizer (for 30 s) 1 min after dye injection. BRL 38227 significantly inhibited OA-induced bronchoconstrictor response (p < 0.01) and plasma leakage in trachea (p < 0.05) and main bronchi (p < 0.05). BRL 38227 also had an inhibitory effect on exogenous histamine- and leukotriene-induced bronchoconstriction and microvascular leakage. However, BRL 38227 did not affect OA-induced histamine release from minced lung tissues in sensitized guinea pigs. We conclude that the allergic bronchoconstrictor response and airway plasma leakage are inhibited by a potassium channel opener, possibly as a result of its effect on the airway smooth muscle and the postcapillary venule level.
Ichinose
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Miura
M
M
Takahashi
T
T
Yamauchi
H
H
Nakajima
N
N
Igarashi
A
A
Ishikawa
J
J
Inoue
H
H
Maeyama
K
K
Watanabe
T
T
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000098:blood supply; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D019806:Cromakalim; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005070:Evans Blue; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D017998:Leukotriene D4 / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D015221:Potassium Channels; D011758:Pyrroles / Q000494:pharmacology*
D000941:Antigens; D001578:Benzopyrans; D001993:Bronchodilator Agents; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D005070:Evans Blue; D017998:Leukotriene D4; D006632:Histamine; D010047:Ovalbumin; D004121:Dimethyl Sulfoxide