Nedocromil sodium inhibits bradykinin- and antigen-induced plasma extravasation in guinea pig airways

This study was designed to investigate the inhibitory effect of Nedocromil sodium (NS) on bradykinin- and antigen-induced plasma extravasation in guinea pig trachea. Plasma extravasation was assessed by photometric measurement of extravasated Evans blue dye after formamide extraction. Pretreatment with NS (0.1, 1, and 10 mg/kg i.v) significantly and dose-dependently reduced bradykinin (inhalation, 0.1 mM, 2 min)-induced plasma extravasation in the presence of neutral endopeptidase inhibitor, phosphoramidon (2.5 mg/kg iv.), in the trachea. Pretreatment with NS (10 mg/kg i.v.) or disodium cromoglycate (DSCG; 10 mg/ kg i.v.) significantly reduced antigen-induced (inhalation of ovalbumin; 5%, 2 min) plasma extravasation in the sensitized guinea pig trachea. Inhibition of the antigen-induced plasma extavasation in the trachea by NS (10 mg/kg i.v.) was significantly greater than the inhibition by DSCG (10 mg/kg i.v.) and similar to the inhibition by pretreatment with a combination of NS and FK224. Pretreatment with the combination of NS and antihistaminic drugs inhibited the antigen-induced plasma extavasation in the trachea more than the antihistaminic drugs alone. However, the inhibition by pretreatment with the combination of NS and antihistaminic drugs did not differ from the inhibition by NS alone. These findings suggest that NS inhibits antigen-induced plasma extravasation, histamine release by mast cells and tachykinin release from sensory nerves activated from bradykinin stimulation in sensitized guinea pig airway.