EFFECTS OF CROMAKALIM (BRL-34915) IN TRACHEA ISOLATED FROM ACTIVELY SENSITIZED GUINEA-PIGS

The effects of cromakalim were examined in tracheal strips isolated fr om normal (unsensitized) guinea-pigs and from animals actively sensiti zed to bovine serum albumin. Sensitized tracheae exhibited hyper-respo nsiveness to KCl, acetylcholine and histamine. In normal and sensitize d tracheae, cromakalim (0.01-10 muM) produced a concentration-related suppression of spontaneous tone. The ability of cromakalim to relax tr acheal strips was reduced when tone was raised by KCl (25 mM), acetylc holine (0.1 mm) or histamine (0.1 mM) and lost against KCl (120 mM)-in duced spasm. Procaine (5 mM) abolished the relaxant effect of cromakal im whilst tetraethylammonium (8 mM) was without effect. These effects were similar in normal and sensitized tissues. Cromakalim (10 muM) pro duced minor alterations of the concentration-effect curves of KCl (1-1 00 mM), acetylcholine (1 nM-1 mM) and histamine (1 nM-1 mM) in normal and sensitized tissues. The results from this pharmacomechanical study do not support the hypothesis that altered properties of cromakalim-s ensitive K+ channels underlie the airway hyper-reactivity induced by a ctive sensitization to bovine serum albumin.