IMMUNE SENSITIZATION AUGMENTS EPITHELIUM-DEPENDENT SPONTANEOUS TONE IN GUINEA-PIG TRACHEALIS

We examined epithelial modulation of tracheal smooth muscle (TSM) resp onsiveness in vitro from guinea pigs receiving active immune sensitiza tion in vivo. Initially, guinea pigs were either ovalbumin sensitized (by aerosol) or sham sensitized with normal saline; TSM responsiveness was assessed isometrically as active tension (AT) after equilibration by electrical field stimulation in vitro. For epithelium-intact (Epi) tissues, sensitization caused an increase in baseline active spontan eous tone (1.89 +/- 0.20 g AT) vs, sham-sensitized tissues (1.18 +/- 0 .20 g AT; P = 0.02). Spontaneous tone in sensitized TSM in which the e pithelium was removed (Epi-) (1.01 +/- 0.14 g AT) was substantially le ss than from Epi+ tissues (P = 0.01) and did not differ from sham-sens itized epithelium-denuded tissues (0.82 +/- 0.24 gAT; P > 0.05). Indom ethacin caused a reduction in spontaneous tone to comparable magnitude for all treatment paradigms. Immune sensitization caused physiologica l reduction in the ability to relax in response to isoproterenol; the concentration of isoproterenol eliciting 50% relaxation of spontaneous tone-was 7.10 +/- 0.13 (-log M) for TSM from sensitized guinea pigs c ompared with 8.20 +/- 0.27 (-log M) for sham-sensitized tissues (P = 0 .006). However, after precontraction with exogenous acetylcholine, rel axation caused by isoproterenol was not affected by either indomethaci n or epithelial removal. Muscarinic responsiveness to acetylcholine wa s augmented by immune sensitization; however, the increase in response to acetylcholine was attenuated by epithelium removal or cyclooxygena se blockade. Our data demonstrate substantial differences in the contr actile and relaxant properties of spontaneous tone in vitro that are 1 ) epithelium dependent and 2) not replicated by contraction with exoge nous agonist in the presence of indomethacin. Our data suggest that th is augmentation of contraction and reduced ability of beta-adrenergic relaxation of spontaneous tone result from secretion of an epithelial- derived contractile factor that is likely a cyclooxygenase derivative.