Vascular leakage induced by exposure to arsenic via increased production of NO, hydroxyl radical and peroxynitrite

Both L-NAME (0.02, 0.1 and 0.5 µmol/site) and DMTU (0.05, 0.2 and 1.2 μmol/site) inhibited the increase in vascular leakage induced by arsenite. However, only high dose (1 μmol/site) of AG significantly attenuated arsenite-induced vascular leakage. In contrast, neither D-NAME (0.02, 0.1 and 0.5 µmol/site) nor AG (0.04 and 0.2 μmol/site) attenuated increased vascular leakage by arsenic. DMTU mixed with L-NAME caused no further inhibition of arsenic-induced vascular leakage by either DMTU or L-NAME. The techniques of India ink and immunostaining were used to demonstrate both vascular labeling and nitrotyrosine staining in tissue treated with arsenic. L-NAME apparently reduced the density of leaky vessels and the levels of peroxynitrite staining induced by arsenite. These results suggest that NO, OH− and peroxynitrite play a role in increased vascular permeability induced by arsenic exposure.