POTASSIUM CHANNEL OPENER, YM-934, INHIBITS NEUROGENIC PLASMA LEAKAGE IN GUINEA-PIG AIRWAYS

The effect of a potassium channel opener, YM 934, on neurogenic airway plasma leakage was examined in anesthetized guinea pigs. Airway plasma leakage was evoked by stimulation of both vagal nerves in the presence of atropine (1 mg/kg, intravenous) and propranolol (1 mg/kg, intravenous), and was measured by extravasation of Evans blue dye (30 mg/kg, intravenous) in trachea (Tr), main bronchi (MB), and central (cIPA) and peripheral intrapulmonary airways (pIPA). Vagal stimulation significantly increased the dye leakage in all portions of the airway. YM 934 (10, 30, and 100 mu g/kg, intravenous) inhibited vagally-induced plasma leakage in Tr, MB, cIPA, and pIPA, and this inhibitory effect of YM 934 was reduced by the ATP-sensitive potassium channel blocker; glibenclamide (25 mg/kg, intravenous). By contrast, YM 934 (100 mu g/kg, intravenous) had no inhibitory effect on exogenous substance P (0.5 and 1 mu g/kg, intravenous)-induced plasma leakage in any parts of the airway These results indicate that YM 934 inhibits airway neurogenic inflammation by modulating the release of neuropeptides from the sensory nerve endings, and that the inhibitory effect can be attributed to the potassium channel opening activity of this compound.