Anoxic injury of endothelial cells increases production of nitric oxide and hydroxyl radicals.
Reactive oxygen radicals have been implicated as mediators of anoxic injury in brain, but the cellular source of these radicals is unknown. In the periphery, there is evidence that endothelial cells play a fundamental role in anoxic tissue injury. The objective of the present study was to examine the response of rat brain endothelial cells to anoxia/reoxygenation injury in vitro. The results demonstrate that brain endothelial cells produce hydroxyl radicals and have increased nitric oxide synthase activity after anoxic injury. The increased production of nitric oxide in the cerebral endothelial cells does not appear to be mediated by an increase in either inducible or constitutive nitric oxide synthase. The radical trap alpha-phenyl-tert-butyl nitrone blocked hydroxyl free radical production, but not nitric oxide. These data suggest that the cerebral microcirculation may be an important site of oxygen free radical production in the brain in ischemic stroke.
Kumar
M
M
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Liu
G J
GJ
Floyd
R A
RA
Grammas
P
P
D000332:Aerobiosis; D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008833:Microcirculation; D017942:Nitric Acid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats
D017665:Hydroxyl Radical; D017942:Nitric Acid; D019001:Nitric Oxide Synthase