Do Perfused Small Caliber Airways of Guinea-pig Release an Epithelium-dependent Relaxing Factor?

Abstract

Summary: The influence of epithelium removal on the effects of contractile substances on airway responsiveness was investigated on the guinea-pig perfused bronchioles. A gentle rubbing of the luminal surface with a pipe cleaner significantly shifted to the left the concentration-response curves evoked by histamine (3 × 10 -12-10 -4 M) and acetylcholine (10 -9-10 -3 M) and decreased the relaxation response to fenoterol (10 -12-2 × 10 -5 M). In contrast, removal of epithelium did not alter the responses to K + (4.7 × 10 -3-1.2 × 10 -1 M), theophylline (10 -8-10 -2 M), sodium nitroprusside (4 x 10 -10-4 × 10 -5 M) or papaverine (10 -4 M). In intact preparations treated with indomethacin (10 -5 M), histamine and acetylcholine induced contractions similar to that produced by rubbed tissues whereas relaxation induced by fenoterol was not modified. 10 -5 M tranylcypromine (inhibitor of prostacyclin synthesis) or 10 -6 M L-NAME (N G Nitro-L-Arginine Methyl Ester, a nitric oxide synthesis inhibitor) did not alter any concentration-response curves. Whereas prostaglandin E 2 had no effect, prostaglandin E 1 (10 -12-10 -5 M) induced concentration-dependent relaxation, indicating that this prostanoid could be an epithelium-derived relaxing factor. These results suggest that epithelium of small caliber airways could release a cyclooxygenase product, namely a prostanoid, involved in the epithelium-dependent modulation in response to contractile drugs.