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 ⨯ 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 ⨯ 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 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. © 1993 Academic Press. All rights reserved.