ROLE OF HYDROXYL RADICAL IN THE STIMULATION OF ARACHIDONIC-ACID RELEASE CAUSED BY H2O2 IN PULMONARY SMOOTH-MUSCLE CELLS - PROTECTIVE EFFECT OF ANION CHANNEL BLOCKER

We sought to investigate role of hydroxyl radical (OH.) in H2O2 caused stimulation of arachidonic acid (AA) release from rabbit pulmonary arterial smooth muscle cells, and to ascertain protective effect of the anion channel blocker DIDS in this phenomenon. Exposure of the smooth muscle cells to the oxidant H2O2 (1 mM) stimulates iron release and enhances AA liberation from the cells. Pretreatment of the cells with either deferoxamine (DFO) or dimethyl thiourea (DMTU) markedly reduces AA release and prevents OH. production without causing any appreciable reduction of iron release caused by H2O2. Simultaneous treatment of either DFO or DMTU with H2O2 significantly reduces AA release, and also prevents OH. production without causing any significant reduction of iron release. In contrast, addition of either DFO or DMTU even 2 min after exposure of the cells to H2O2 does not cause any significant reduction of AA release, OH. production and iron release. Pretreatment of the cells with DIDS markedly reduces AA release caused by H2O2 without producing any discernible reduction of iron release, and OH. production.