The effect of non-isotonic solutions on human isolated airway smooth muscle

In patients with asthma, bronchoconstriction can be provoked by the inhalation of aerosols of non-isotonic solutions. In order to determine if this bronchoconstriction results from a direct effect on airway smooth muscle we decided to examine the effects of non-isotonic solutions on the resting tone of human isolated bronchi and on responses to carbachol, histamine and field stimulation. Human bronchi were obtained from thoracotomy and dose-response relationships for each agonist were obtained for bronchial rings suspended in isotonic Krebs-Henseleit solution (290 mOsm). A second curve was then obtained with half the rings immersed in a solution made hypotonic (145 mOsm) or hypertonic (440 mOsm) by the addition of NaCl or salts and glucose. The other half remained in isotonic solutions as controls. In a separate series of experiments, field stimulation responses to a submaximal frequency (15 Hz) were measured before and after a change from isotonic to non-isotonic bathing solution. The resting tone of the preparations was transiently reduced by hypertonic solutions and increased by hypotonic solutions. Contractile responses to agonists were significantly diminished by non-isotonic solutions. Agonist potency was unaffected by hypertonic solutions but the potency of carbachol was reduced by hypotonic solutions. Responses to field stimulation were unaffected by the hypertonic solution but reduced by the hypotonic solution. We conclude that the bronchoconstrictor actions of non-isotonic solutions and their effects on airway reactivity are unlikely to be due to direct effects on airway smooth muscle.