Effect of histamine and methacholine on guinea pig tracheal permeability to HRP

The effects of histamine, methacholine, and ether on the permeability of the respiratory mucosa to macromolecules were investigated employing a radioimmunoassay and histochemical techniques to monitor movement of horseradish peroxidase (HRP) from airway lumen to blood. We found that 0.08% of the dose of HRP instilled into guinea pig tracheas was present in the blood volume at 10 min, and plasma HRP levels increased at a rate of 0.0036% instilled dose/min thereafter. After inhalation challenge, significant increases in plasma rates of accumulation of HRP were recorded for the histamine, methacholine, and ether groups, whereas no change in rate was noted for the control (Tyrode's) group. Electron micrographs of tracheal sections showed HRP penetration into the intercellular spaces of the epithelium after histamine, methacoline, or ether exposure but no penetration in the Tyrode's group. We conclude that, like ether, histamine and methacholine increase tracheobronchial permeability and this effect is most likely mediated by a functional change in the epithelial tight junction.