Hydrogen peroxide-induced potentiation of contractile responses in isolated rat airways.
We hypothesized that metabolites of O2 may play a role in the development of airway hyperreactivity and undertook this study to examine the effects of one of these metabolites, hydrogen peroxide (H2O2), on electrical field stimulation-induced contractile responses of isolated rat intrapulmonary bronchi. Exposure to H2O2 (1 mM) elicited a transient contractile response with a peak response equivalent to 18.1 +/- 2.0% of the reference contraction obtained to electrical stimulation. The H2O2-induced contraction was attenuated by pretreatment of tissues with indomethacin and superoxide dismutase, but abolished by catalase and mianserin. Subsequent to H2O2 exposure, electrical field stimulation-induced contractile responses were potentiated (P less than 0.0001), whereas acetylcholine-induced contractions were not. The potentiating effects of H2O2 were inhibited by catalase and mianserin. Addition of 5-hydroxytryptamine (5-HT) to the bath similarly potentiated contractions to electrical stimulation (P less than 0.0001). Together, these results are consistent with a role for 5-HT in H2O2-induced contraction and the subsequent potentiation of airway smooth muscle contraction elicited by cholinergic nerve activation. Thus endogenous metabolites of O2 may be important in modulating airway smooth muscle tone.
Szarek
J L
JL
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
Schmidt
N L
NL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D004558:Electric Stimulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D008803:Mianserin; D012701:Serotonin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D007213:Indomethacin