Effects of hyperosmolarity and airway epithelial ion transport inhibitors on sodium nitroprusside-induced relaxation of guinea pig trachea

Abstract

Increased airway surface osmolarity has been shown to abolish the airway relaxant effects of inhaled nitric oxide. We have investigated the effects of increased airway surface osmolarity on airway relaxation induced by nitric oxide. The physiological responses, obtained by a guinea pig tracheal perfusion method, were compared to the ion content of the tracheal tissues, and the effects of amiloride or furosemide were studied. Hyperosmolarity decreased the ability of sodium nitroprusside (SNP) to relax carbachol-constricted trachea. Light microscopy showed shrinkage of the epithelial cells and X-ray microanalysis showed increased epithelial ion content under conditions of intraluminal hyperosmolarity, suggesting dehydration of the epithelium. Amiloride treatment reduced the increase in epithelial ion content but had no effect on shrinkage or SNP-induced relaxation. Furosemide had no effect on the altered ion content, shrinkage, or on SNP-induced relaxation. In conclusion, neither amiloride nor furosemide can counteract the shrinkage of the airway wall induced by increased osmolarity in the lumen of guinea pig trachea in vitro, nor can they affect the reduction in relaxing response to the NO-donor SNP.