Release of epithelium-derived relaxing factor (EpDRF) by hyperosmolar "jump."
Fedan-JS; Dowdy-JA; Wu-D; Van Scott-MR
Am J Respir Crit Care Med 2003 Apr; 167(7):A399
Exercise-induced asthma may be stimulated by an increase in airway surface liquid osmolarity. Inhaled hyperosmolar solutions cause obstruction in asthmatics. In guinea-pig perfused trachea contracted with methacholine (MCh), elevation of mucosal osmolarity using diverse osmolytes relaxes the smooth muscle. Chemically-diverse osmolytes are equiactive in this regard. We examined whether EpDRF is released only by hyperosmolar addition to normosmolar solution, or in response to incremental increase in osmolarity (hyperosmolar "jump"). In MCh-contracted tracheas, perfusion of the lumen with water in place of Krebs solution (KS) evoked a contractile response which declined to the MCh-induced level. Rapid re-perfusion with KS evoked a transient relaxation. At the new steady state, elevation of mucosal KS osmolarity with mannitol (M; 240 mosM) relaxed the trachea. To evaluate the role of ion transport in the response to hyperosmolar "jump" tracheas were perfused with solutions of isosmolar M, NMDG gluconate, urea, NaCI and KCI after hyptonic challenge with water. Like KS, rapid replacement of mucosal water with each of these osmolytes resulted in large, transient relaxation responses. The osmolyte-nonspecificity of this effect indicates that flux of the major ions across the apical membrane is not involved in causing relaxation. For all five osmolytes, upon stabilization of the response to a given isosmolar osmolyte, mucosal addition of 240 mosM of the same osmolyte to the isosmolar solution triggered a relaxation response. These results indicate that EpDRF is released in response to incremental increases in osmolarity, regardless of the absolute osmolarity existing at the time the change occurs. The osmosensor in epithelial cells which mediates this response is unknown.
Pulmonary-system-disorders; Respiratory-system-disorders; Airway-obstruction; Airway-resistance; Muscles; In-vitro-study
Abstract; Conference/Symposia Proceedings
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003