Products of cyclooxygenase mediate the responses of the guinea pig trachea to hydrogen peroxide

Abstract

The role of products of cyclooxygenase was investigated in the responses of isolated airways to H2O2. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers, and isometric tension was recorded. Under basal conditions, H2O2 induced indomethacin-sensitive contractions, which were larger in preparations without than in those with epithelium; the difference was abolished by inhibitors of thromboxane synthase or thromboxane A2 receptors. During contractions to acetylcholine, low concentrations of H2O2 induced relaxation in preparations with but had no significant effect in those without epithelium. At higher concentrations of H2O2, the epithelium-dependent relaxation was attenuated but an epithelium-independent relaxation appeared. The epithelium-dependent but not the epithelium-independent responses to H2O2 were blocked by indomethacin. Under basal conditions, prostaglandin E2 (PGE2; < or = 10(-7) M), U-46619, prostaglandin PGF2 alpha (PGF2 alpha), prostaglandin PGD2 (PGD2), and prostacyclin (PGI2) caused contractions. During contractions to acetylcholine, PGE2 induced larger relaxations in preparations with than in those without epithelium. Radioimmunoassay revealed that lower concentrations of H2O2 predominantly increased the release of PGE2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha); in preparations without epithelium, the release of thromboxane B2 was augmented also. At higher concentrations of H2O2, the release of PGE2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha, and thromboxane B2 increased in preparations with and without epithelium. These findings demonstrate that the responses of the guinea pig trachea to H2O2 are mediated mainly by products of cyclooxygenase and that the effects of H2O2 are modulated by the epithelium.

Effects of Various Reactive Oxygen Species on the Guinea Pig Trachea and Its Epithelium

“…Moreover, it was found that of the two isoforms, the constitutive COX-1 and the inducible COX-2, only the latter is activated by H 2 O 2 (50, 51) and superoxide (50). The COX inhibitor indomethacin relaxed both the intact and epithelium-denuded trachea in the present as well as in the earlier experiments (20). The indomethacin induced relaxation of the intact trachea was significantly larger than that of the epithelium-denuded trachea.…”

“…As described earlier, there are species variations among the responses of airways to H2O2: contraction in bovine (21), cat (19) and horse (27) trachea, relaxation in rabbit (17) (also by hydroxyl radical (26)) and dog trachea (18) and biphasic response in guinea pig trachea (16,20). On long lasting contact of tissues with H 2 O 2 , FeSO 4 /H 2 O 2 and FeSO4/ascorbic acid, the contraction not only faded progressively with time but also a significant relaxation appeared, suggesting a biphasic character of the response in the present study.…”

“…Later existence of species differences was demonstrated. H2O2 was shown to relax the rabbit (17) and dog (18) trachea, contract the cat trachea (19) and cause biphasic effect on the guinea pig trachea (20). The effects of H2O2 are generally considered to be modulated by cyclooxygenase inhibitors or epithelium removal (16, 21 -25).…”

“…The effects of H2O2 are generally considered to be modulated by cyclooxygenase inhibitors or epithelium removal (16, 21 -25). Several studies investigating the role of prostaglandins in the mediation of the effects of H2O2 came to contradictory conclusions (16,20) and pointed to marked interspecies differences (16,18,20,26,27).…”

“…Although there are many studies focusing on the effect of H2O2 on isolated trachea or bronchi of various animal species: rat (22), cow (21), ferret (28), rabbit (17), guinea pig (16,17,20,29), human (25), less were done on the effects of ozone (guinea pig trachea (30), feline bronchi (31)), hypochlorous acid (guinea pig trachea (32,33)), hydroxyl radical (rabbit trachea (26)) and xanthine /xanthine oxidase (guinea pig airways in vivo (34) and cat bronchi in vitro (35)). The lack of comprehensive studies that would compare the effects of long-lasting contact of systems generating hydroxyl radical and superoxide anion on the tone of the guinea pig trachea in the presence or absence of epithelium with that of H 2 O 2 on the same tissue of a single animal species prompted us to compare them in guinea pig trachea.…”