Do perfused small caliber airways of guinea-pig release an epithelium-dependent relaxing factor?

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 x 10(-12)-10(-4) M) and acetylcholine (10(-9)-10(-3) M) and decreased the relaxation response to fenoterol (10(-12)-2 x 10(-5) M). In contrast, removal of epithelium did not alter the responses to K+ (4.7 x 10(-3)-1.2 x 10(-1) M), theophylline (10(-8)-10(-2) M), sodium nitroprusside (4 x 10(-10)-4 x 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 (NG Nitro-L-Arginine Methyl Ester, a nitric oxide synthesis inhibitor) did not alter any concentration-response curves. Whereas prostaglandin E2 had no effect, prostaglandin E1 (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.