SENSITIZATION DECREASES RELAXATION IN HUMAN ISOLATED AIRWAYS

Passively sensitized human isolated airways provide an opportunity to study some aspects of bronchial hyperresponsiveness in vitro. Since it has been suggested that excessive airway narrowing could be due to im paired relaxation, we examined the effect of a variety of agents produ cing relaxation via different mechanisms, i.e., verapamil and lemakali m (a calcium channel antagonist and a potassium channel opener, respec tively) and isoproterenol, forskolin, and dibutyryl cAMP (modulators o f the beta-adrenoceptor signal transduction pathway). Human bronchial rings, obtained at thoracotomy, were passively sensitized by incubatio n in serum from atopic asthmatic patients, and control rings were incu bated in serum from nonatopic subjects. We also studied bronchial ring s from five spontaneously sensitized human lung specimens. Responses t o the relaxant compounds were measured isometrically. Passive sensitiz ation significantly decreased the efficacy of verapamil in maximally c ontracted tissues from 60 +/- 10 to 45 +/- 7% of the maximal carbachol response (n = 6, p < 0.05) and that of lemakalim from 51 +/- 16 to 38 +/- 14% (n = 7, p < 0.05) in tissues at baseline tone. Similarly, spo ntaneously sensitized tissues relaxed less to lemakalim (64 +/-6% of t he maximal response to isoproterenol, n = 5, p < 0.05) than did nonsen sitized tissues (80 +/- 4%). Sensitization did not alter responses to isoproterenol, forskolin, and dibutyryl cAMP. We conclude that sensiti zation of human isolated airways reduces relaxation responses that dep end upon activation of ion channels but not those that depend upon act ivation of beta-adrenoceptors and transduction processes directly coup led to these receptors.