Am. J. Respir. Crit. Care Med., Vol 150, No. 2, Aug 1994, 388-393.
Antigen-induced airway responses are inhibited by a potassium channel opener
M Ichinose, M Miura, T Takahashi, H Yamauchi, N Nakajima, A Igarashi, J Ishikawa, H Inoue, K Maeyama and T Watanabe
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
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.
