Asthmatics experience obstruction during exercise, due to an increase in the osmolarity of the airway surface liquid, and after inhalation of HO aerosols. The mechanism of the response to changes in osmolarity was examined by comparing the effects of mucosal HO (osmolyte added to Krebs solution) and I0 (osmolyte added to water) solutions on mechanical responses of serosal methacholine (3xIO.7 M)-contracted perfused trachea (PT) and short circuit current (Isc) responses of the epithelium. HO D-mannitol (D-M), NMDG-gluconate (N-G), urea (U), NaCl or KCI caused relaxation of the PT. Perfusion with I0 solutions of these osmolytes caused variable responses (contraction, contraction/relaxation, no response, or, rarely, relaxation), but subsequent HO addition of the same osmolyte to the I0 perfusate always triggered relaxation. HO D-M, N-G and U decreased Isc, whereas HO NaCI and KCI increased Isc. I0 solutions of the three ionic osmolytes, N-G, NaCI and KCI, decreased Isc, but subsequent HO addition of these osmolytes stimulated Isc responses similar to those obtained after adding them to Krebs solution. Thus, the mechanical responses to HO or I0 osmolyte solutions were independent of the ionic nature or permeance of the solute. Relaxation was associated with an increase in osmolarity. The bioelectric effects of I0 solutions of osmolytes were similar, but those of HO solutions were agent-specific.
The FASEB Journal, Experimental Biology 2003, San Diego, California, April 11-15, 2003