Elevated levels of arsenite, the trivalent form of arsenic, in drinking water correlate with increased vascular disease and vessel remodeling. Previous studies from the laboratory demonstrated that environmentally relevant concentrations of arsenite caused oxidant-dependent increases in nuclear transcription factor levels in cultured porcine vascular endothelial cells (Barchowsky et al., Free Radical Biology & Medicine, 21:6; p.783-790, 1996). The current studies characterized the reactive species generated in these cells exposed to levels of arsenite just sufficient to signal cells. These exposures did not deplete ATP, nor did they affect basal or bradykinin-stimulated intracellular free Ca2+ levels, indicating that they were not lethal. Electron Paramagnetic Resonance (EPR) and spin trapping with carboxy-PTIO (cPTIO) demonstrated that 5 M or less of arsenite did not increase NO levels over a 30 minute time period relative to stimulation by bradykinin. However, these same levels of arsenite rapidly increase both oxygen consumption and superoxide formation, as measured by EPR oximetry and spin trapping with DMPO, respectively. Pre-treatment of the cells with diphenyleneiodonium (DPI), rotenone, or cyanide attenuated arsenite-stimulated oxygen consumption. Arsenite increased release of H2O2, measured as oxidation of homovanillic acid, with the same time and dose dependence. These data suggest that superoxide and H2O2 are the predominant reactive species produced by endothelial cells following arsenite exposures that stimulate cell signaling and activate transcription factors.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011602-04
Application #
6206499
Study Section
Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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