Am. J. Respir. Crit. Care Med.,
Volume 156, Number 3, September 1997, 723-727
Effect of 
2-agonists on Histamine-induced Airway
Microvascular Leakage in Ozone-exposed Guinea Pigs
HIROMASA
INOUE,
HISAMICHI
AIZAWA,
KOICHIRO
MATSUMOTO,
MUTSUMI
SHIGYO,
SHOHEI
TAKATA,
MASATO
HARA,
and
NOBUYUKI
HARA
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan
2-adrenergic agonists exhibit antipermeability effects in the airways. However, it is not known
whether 2-agonists have this beneficial effect in airway mucosa that is already inflamed. We evaluated the effects of two inhaled 2-agonists, salbutamol and formoterol, on the histamine-induced
bronchoconstriction and plasma extravasation in the airways of guinea pigs with or without ozone
exposure. Total pulmonary resistance (RL) was measured before and after histamine inhalation in
anesthetized animals that were pretreated with inhaled salbutamol, formoterol, or saline. Plasma extravasation in the airways was measured using Evans blue dye. In the control animals not exposed to
ozone, salbutamol and formoterol each significantly reduced both the histamine-induced bronchoconstriction and the plasma extravasation in the trachea and main bronchi. In the ozone-exposed animals, the increase in RL after histamine was greater than that in control animals. Salbutamol and formoterol each significantly reduced histamine-induced bronchoconstriction, even in the ozone-exposed
animals. Salbutamol did not affect the histamine-induced plasma extravasation, whereas formoterol
reduced the plasma extravasation in the main bronchi, but not in the trachea, of the animals exposed
to ozone. These results suggest that the anti-inflammatory properties of formoterol in inflamed airways may contribute to the beneficial effects in the treatment of airway inflammation.
