Ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to attenuate eicosanoid-induced airflow obstruction and airway microvascular leakage.
Beta-2 adrenoceptor agonists are widely used as bronchodilators in the treatment of asthma mainly via inhalation. In the present study, we evaluated the ability of inhaled procaterol, a beta 2 adrenoceptor agonist, to reduce eicosanoid-induced airway microvascular leakage, and compared the ability with its inhibitory effect against bronchoconstriction. Tracheostomized guinea-pigs were given aerosolized procaterol (10 or 100 micrograms/ml) for 10 min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20 mg/kg) was given i.v. One minute later, 2 nmol/kg leukotriene D4 (LTD4), 50 nmol/kg U-46619, a thromboxane A2 mimetic, or vehicle was administered i.v. LTD4- or U-46619-induced increase in lung resistance was measured for 6 min. After removing the lungs, the amount of extravasated Evans Blue due in the lower airways was examined as an index of microvascular leakage. Inhaled procaterol significantly attenuated increases in both lung resistance and Evans Blue dye extravasation caused by these eicosanoids. The degree of inhibition was almost complete for lung resistance (approximately 90%), but it was only partial (range 18.5-61.2%) for the dye extravasation. No significant changes in mean systemic blood pressure and in heart rate was observed after an inhalation of 10 micrograms/ml procaterol. These results suggest that inhaled beta 2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation.
Tokuyama
K
K
Department of Pediatrics, Gunma University School of Medicine, Gunma, Japan.
Arakawa
H
H
Mochizuki
H
H
Morikawa
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000402:Airway Obstruction / Q000139:chemically induced; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D015777:Eicosanoids / Q000494:pharmacology*; D005070:Evans Blue; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017265:Procaterol / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012123:Pulmonary Ventilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D015777:Eicosanoids; D005070:Evans Blue; D017265:Procaterol