The influence of epithelium on the responsiveness of guinea-pig trachea to -adrenergic agonist and antagonist.

BACKGROUND

There is controversy regarding bronchial responsiveness to b2-agonist drugs in asthma. Epithelial shedding in the airways is a pathological feature of asthma. Therefore, the present study focused on the effect of epithelial denudation of guinea pig tracheal chains in response to isoprenaline and b-adrenergic receptor blockade.

MATERIAL/METHODS: In control (group 1, n=10), epithelium-denuded (group 2, n=10), and epithelium-denuded + epithelial cell (group 3 n=6) we measured the responses of tracheal chains to cumulative concentrations of isoprenaline (I) in the absence and presence of 10 nM propranolol, and the value of EC50I was calculated. The propranolol blockade (CR-1) was calculated as the ratio of post propranolol EC50I to initial EC50I.

RESULTS

The tracheal responses to isoprenaline (EC50I) in groups 2 and 3 was significantly higher than in the controls (p<0.05 for both cases), but was not significantly different between the groups 2 and 3. The values of CR-1 in group 2 only was significantly higher than the controls (p<0.001). The mean CR-1 in group 3 was significantly lower than in group 2 (p<0.01). There was significant negative correlation between EC50I and CR-1 in all three groups (p=0.002).

CONCLUSIONS

The results of this study indicate increased tracheal response to a b-adrenergic stimulating drug in both groups 1 and 2, and enhancement of b-adrenergic blockade by propranolol only in group 1. These results may indicate some of the mechanisms of asthma aggravation by b2-antagonist drugs.