Protection of perfused lung from oxidant injury by inhibitors of anion exchange

摘要: Hyperoxic lung injury is enhanced in isolated perfused lungs (IPL) the presence of L-arginine. Reactive O2 species such as superoxide anion (O2-.) produced during hyperoxia are known to react with nitric oxide form strong oxidant peroxynitrite. The appearance O2-. red blood cell membranes vitro and buffer-perfused preparations can be inhibited by stilbene compound 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) DIDS also inhibits exchange across membrane regulated a family proteins (AE). In this study, we hypothesized that inhibitors would prevent from L-arginine (O2 + L-Arg) decreasing flux into vascular space IPL. We found both structurally distinct transport blocker, dipyridamole, protected rabbit IPL pulmonary hypertension edema L-Arg. protective effect was associated increased nitrite concentrations perfusate. Protection conferred when sodium bicarbonate perfusion buffer replaced either thiosulfate or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic (HEPES). HEPES-containing buffer, protection diminished detection reducing activity consistent space. Western blot analysis protein immunocytochemical staining sections using antibodies against AE1 mouse gastric AE2 peptide showed contains antigenically similar AE2. These data suggest possibility inhibition AE other transporters may play an important role mediating oxidative injury.