Effect of the K+(ATP) channel opener, KC0912, on baseline and allergen induced airway hyperresponsiveness in allergic rabbits

The effect of the adenosine triphosphate sensitive K+ (K-ATP) channel opener (3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-piperidinyl)-N-phenyl-1-benzopyran-6-sulphonamide (KC0912) on airway hyperresponsiveness induced using either a combination of allergen immunization (i.p.) followed by aerosol allergen challenge or immunization alone was investigated. Rabbits were immunized with Alternaria tenuis for the first 3 months of life. Airway responsiveness to histamine was measured 24 h before and after A. tenuis aerosol challenge. Fifteen minutes before the second challenge, rabbits were pre-treated with 10 mug of KC0912 or vehicle by inhalation. Allergen challenge induced airway hyperresponsiveness in vehicle pre-treated rabbits and pre-treatment with KC0912 abolished the airway hyperresponsiveness. The effect of KC0912 (10 mug) or vehicle on baseline airway hyperresponsiveness to the adenosine A(1) receptor agonist, cyclopentyl adenosine (CPA), induced by immunization with A. tenuis alone, was also assessed. Rabbits, immunized with A. tenuis alone, exhibited baseline airway hyperresponsiveness as demonstrated by an increase in airway resistance to CPA. Treatment with KC0912 did not alter the allergen-induced airway responsiveness to CPA. This study demonstrates that KC0912 can inhibit allergen-induced exacerbations of airway hyperresponsiveness. (C) 2003 Elsevier B.V. All rights reserved.