The role played by the epithelium in H(2)O(2)-induced modulation of the mechanical responses induced by acetylcholine (ACh) in rabbit intrapulmonary bronchioles was investigated in epithelium-intact and -denuded strips. 2. When ACh (3 microM) was applied intermittently, H(2)O(2) (30 microM) enhanced the ACh-induced contractions in epithelium-intact strips. In contrast, in epithelium-denuded strips H(2)O(2) (30 microM) inhibited such contractions. At higher concentrations, H(2)O(2) concentration-dependently attenuated the ACh-induced contractions in both epithelium-intact and -denuded strips, its action being more potent in the latter strips than in the former. 3. Diclofenac (a cyclo-oxygenase inhibitor; 3 microM) reduced the H(2)O(2)-induced enhancement of ACh-contractions in epithelium-intact strips but had no effect on the H(2)O(2)-induced inhibition in epithelium-denuded strips. N(G)-nitro-L-arginine did not alter the effect of H(2)O(2) on ACh-induced contractions in epithelium-intact strips. 4. Catalase (500 u ml(-1)) completely blocked both H(2)O(2)-induced effects on ACh-contractions (enhancement and inhibition). Neither superoxide dismutase (200 u ml(-1)) nor deferoxamine (0.5 mM) had any effect on H(2)O(2)-induced inhibition in epithelium-denuded strips. 5. Aminotriazole (an inhibitor of catalase; 50 mM) significantly potentiated the H(2)O(2)-induced inhibition of ACh-contractions in epithelium-intact strips but not in epithelium-denuded strips. 6. The density ratio for catalase (epithelium-intact over -denuded strips) analysed by Western blot was about 2.1, suggesting that epithelium contains more catalase than smooth muscle. 7. It is concluded that in rabbit intrapulmonary bronchioles, H(2)O(2) has dual actions on ACh-contractions. It is suggested that the epithelium may act as a powerful biochemical barrier via both the action of catalase (scavenging H(2)O(2)) and the release of bronchoconstrictor prostaglandins, thus attenuating the H(2)O(2)-induced modulation of ACh-contractions.
