Nedocromil sodium inhibits hypertonic saline-induced plasma extravasation in guinea pig airways

We investigated the potential of nedocromil sodium (NS) to reduce neurogenic plasma extravasation induced by hypertonic saline in guinea pig airways. Plasma extravasation was assessed by photometric measurement of extravasated Evans blue after formamide extraction. Hypertonic saline was delivered to anesthetized, artificially ventilated guinea pigs through a tracheal cannula. Inhalation of hypertonic saline for 2 min increased Evans blue dye extravasation in the trachea in a concentration-dependent (0.9,5,10,15 and 20 %) manner. The increase in plasma extravasation induced by hypertonic saline (15 %) was significantly reduced by pretreatment with NS (10 mg/kg, i. v.). The inhibition of plasma extravasation by NS (10 mg/kg, i. v.) alone was not different from the inhibition induced by the combination of NS and the bradykinin B-2 receptor antagonist, HOE140 (0.1 mu mol/kg, i. v.) or HOE140 (0.1 mu mol/kg, i. v.) alone. However, pretreatment with the combination of NS (10 mg/kg, i. v.) and the tachykinin NK1 and NK2 receptor antagonist, FK224 (3.2 mg/kg, i. v.) abolished the increase in plasma extravasation induced by hypertonic saline (15 %). The increase in plasma extravasation induced by inhalation of bradykinin (0.1 mM) for 2 min was abolished by pretreatment with NS (10 mg/kg, i. v.). These findings suggest that NS reduced the hypertonic saline-induced plasma extravasation by inhibiting bradykinin-dependent neurogenic inflammation in guinea pig airways.