Epithelium-dependent relaxation responses of guinea-pig isolated, perfused trachea to hypertonic solution involves carbon monoxide (CO).
Fedan-JS; Dowdy-J; Reasor-MJ; Van Scott-MR; Johnston-RA
Am J Respir Crit Care Med 2002 Apr; 165(8)(Suppl):A65
Application of hypertonic solution to the mucosal surface of the guinea-pig isolated, perfused trachea (IPT) elicits epithelium-dependent relaxation of airway smooth muscle via epithelium-derived relaxing factor (EpDRF), the identity of which is unknown. The purpose of this study was to examine whether CO mediates smooth muscle relaxation. After contracting the smooth muscle with serosally-applied methacoline (3 x 10-7 M), the PT was challenged with mucosally-administered D-mannitol (D-M; 120-160 mosM), a non-permeant osmolyte. The effects of inhibitors on the response to D-M were examined. Neither cyclooxygenase inhibition with indomethacin (3x10-6 M; 30 min) nor injibition of nitric oxide (NO) synthase with Nw-nitro-L-arginine methyl ester (L-NAME; 10-4 M; 30 min) affected the response to D-M, indicating that neither prostanoids nor NO are involved. Upon addition of the CO scavenger, hemoglobin (Hb; 10-6M; 30 min) the IPT developed small contractile responses. In the presence of Hb the relaxation to D-M was inhibited significantly. Neither Hb nor ZnPP abolished completely the relaxation response to D-M. These results suggest that epithelium-derived CO participated in the hypertonicity-induced relaxation of the trachea.
In-vitro-studies; Pulmonary-system; Cell-function; Cellular-reactions; Muscle-cells; Muscle-function; Muscles
Conference/Symposia Proceedings; Abstract
American Journal of Respiratory and Critical Care Medicine, 2002 International Conference, The American Thoracic Society, Atlanta Georgia, May 17-22, 2002