Attenuation of free radical generation during reversible focal cerebral ischemia with the nitric oxide inhibitor, L-NAME (L-N(G)-nitro-L-arginine methyl ester).
The role of oxygen free radical generation during reversible focal cerebral ischemia and its relationship to nitric oxide mediated mechanisms were examined. In this study, a left frontal cortex microdialysis probe was placed into the previously defined ischemic penumbra region and perfused with a salicylate/CSF solution in the presence or absence of the nitric oxide synthase (NOS) inhibitor L-NAME. Rats were then subjected to transient left hemisphere focal cerebral ischemia. Dialysate was collected at baseline and during the ischemic/reperfusion phase, and the hydroxylation products of salicylate were measured by HPLC with electrochemical detection. A significant elevation of free radical adduct formation was observed in the penumbra region during ischemia/reperfusion. This elevation was significantly attenuated by L-NAME during the reperfusion phase. Elevation of free radical adduct formation within the penumbra region during cerebral ischemia/reperfusion may be mediated in part by NOS-dependent mechanisms.
Solenski
N J
NJ
Department of Neurology, University of Virginia, Charlottesville, VA, USA. njs2j@virginia.edu
Kwan
A
A
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019579:Neocortex / Q000098:blood supply / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism
D004791:Enzyme Inhibitors; D005609:Free Radicals; C056856:2,3-dimethoxy-5-methyl-6-undecyl-1,4-benzoquinol; D014451:Ubiquinone; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester