Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation.
BACKGROUND
Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation.


OBJECTIVE
We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation.


METHODS
Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways.


RESULTS
A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels.


CONCLUSIONS
Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.
Mirza
Z N
ZN
Department of Paediatrics, Gunma University School of Medicine, Maebashi, Japan.
Tokuyama
K
K
Arakawa
H
H
Kato
M
M
Mochizuki
H
H
Morikawa
A
A
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000098:blood supply / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects*; D005070:Evans Blue; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D017265:Procaterol / Q000494:pharmacology*; D012137:Respiratory System / Q000098:blood supply*; D014132:Trachea / Q000098:blood supply / Q000473:pathology
D000318:Adrenergic beta-Agonists; D005070:Evans Blue; D006632:Histamine; D010047:Ovalbumin; D017265:Procaterol