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

被引:27
作者
NozikGrayck, E
Piantadosi, CA
VanAdelsberg, J
Alper, SL
Huang, YCT
机构
[1] DUKE UNIV, MED CTR, DEPT MED, DURHAM, NC 27710 USA
[2] COLUMBIA UNIV, MED CTR, DEPT MED, NEW YORK, NY 10032 USA
[3] BETH ISRAEL HOSP, DEPT MED, BOSTON, MA 02215 USA
关键词
anion exchange protein; L-arginine; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; superoxide; oxygen;
D O I
10.1152/ajplung.1997.273.2.L296
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Hyperoxic lung injury is enhanced in isolated perfused lungs (IPL) in the presence of L-arginine. Reactive O-2 species such as superoxide anion (O-2(-).) produced during hyperoxia are known to react with nitric oxide to form the strong oxidant species peroxynitrite. The appearance df O; in red blood cell membranes in vitro and in buffer-perfused lung preparations can be inhibited by the stilbene compound 4,4'-diisothiocyanostilbene-2,2 '-disulfonic acid (DIDS). DIDS also inhibits anion exchange across the cell membrane regulated by a family of anion exchange proteins (AE). In this study, we hypothesized that anion exchange inhibitors would prevent lung injury from hyperoxia and L-arginine (O-2 + L-Arg) by decreasing O-2(-). flux into the vascular space of the IPL. WE found that both DIDS and a structurally distinct anion transport blocker, dipyridamole, protected the rabbit IPL from pulmonary hypertension and edema produced by O-2 + L-Arg. The protective effect was associated with increased nitrite concentrations in the perfusate. Protection also was conferred when sodium bicarbonate in the perfusion buffer was replaced with either sodium thiosulfate or N-2-hydroxyethylpiperazine-N'-2-ethanesul-fonic acid (HEPES). In lungs perfused with thiosulfate or HEPES-containing buffer, protection from O-2 and L-arginine was also associated with diminished detection of reducing activity consistent with O-2(-). in the vascular space. Western blot analysis of lung protein and immunocytochemical staining of lung sections using antibodies against rabbit red blood cell AE1 and mouse gastric AE2 peptide showed that lung contains membrane protein antigenically similar to gastric AE2. These data suggest the possibility that inhibition of AE or other anion transporters may play an important role in mediating oxidative lung injury.
引用
收藏
页码:L296 / L304
页数:9
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