Ability of inhaled procaterol, a β32 adrenoceptor agonist, to attenuate eicosanoid-induced airflow obstruction and airway microvascular leakage

Authors


Dr K. Tokuyama, Department of Pediatrics, Gunma University School of Medicine, 3–39–15 Showa-machi, Macbashi, Gunma 371. Japan.

Summary

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 β2 adrenoceptor agonist, to reduce eicosanoid-induced airway micro-vascular leakage, and compared the ability with its inhibitory effect against bron-choconstriction. Tracheostomized guinea-pigs were given aerosolized procaterol (10 or 100 μg/ml) for 10min under spontaneous breathing. Immediately after the end of inhalation, the animals were mechanically ventilated. Fourteen minutes after the end of inhalation, Evans blue dye (20mg/kg) was given i.v. One minute later, 2nmol/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 10μg/ml procaterol. These results suggest that inhaled β2 adrenoceptor agonists may reduce airway microvascular leakage caused by inflammatory mediators such as eicosanoids without affecting systemic circulation. However, these agonists may attenuate airway microvascular leakage only partially even in doses which can inhibit bronchoconstric-tion almost completely.

Ancillary