Sensitization Decreases Relaxation in Human Isolated Airways

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Abstract
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 impaired relaxation, we examined the effect of a variety of agents producing relaxation via different mechanisms, i.e., verapamil and lemakalim (a calcium channel antagonist and a potassium channel opener, respectively) and isoproterenol, forskolin, and dibutyryl cAMP (modulators of the beta-adrenoceptor signal transduction pathway). Human bronchial rings, obtained at thoracotomy, were passively sensitized by incubation in serum from atopic asthmatic patients, and control rings were incubated in serum from nonatopic subjects. We also studied bronchial rings from five spontaneously sensitized human lung specimens. Responses to the relaxant compounds were measured isometrically. Passive sensitization significantly decreased the efficacy of verapamil in maximally contracted 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, spontaneously sensitized tissues relaxed less to lemakalim (64 +/- 6% of the maximal response to isoproterenol, n = 5, p < 0.05) than did nonsensitized tissues (80 +/- 4%). Sensitization did not alter responses to isoproterenol, forskolin, and dibutyryl cAMP. We conclude that sensitization of human isolated airways reduces relaxation responses that depend upon activation of ion channels but not those that depend upon activation of beta-adrenoceptors and transduction processes directly coupled to these receptors.