Nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester decreases ischemic damage in reversible focal cerebral ischemia in hyperglycemic rats.
We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic metabolism of nitric oxide. We used magnetic resonance imaging (MRI) techniques to measure neuronal and cerebrovascular injury in a 2-h transient focal cerebral ischemia model in normoglycemic and hyperglycemic rats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Compared to normoglycemia, preexisting hyperglycemia increased the volume of brain tissue exhibiting hyperintensity in diffusion weighted MRI (DWI) by factors of 5.6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar increase in tissue volumes exhibiting hyperintense signal in T2-weighted MRI (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume MRI indicated a large focal no-reflow zone in hyperglycemic rats. Treatment with L-NAME eliminated the no-reflow zone in the hyperglycemic rats, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperintensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thus, nitric oxide is an important mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infarct volume.
Quast
M J
MJ
Marine Biomedical Institute, University of Texas Medical Branch at Galveston 77555-0843, USA.
Wei
J
J
Huang
N C
NC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008991:Monitoring, Physiologic; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D016548:Prosencephalon / Q000098:blood supply / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D013194:Staining and Labeling; D013778:Tetrazolium Salts; D013997:Time Factors
D013778:Tetrazolium Salts; D009569:Nitric Oxide; C009591:triphenyltetrazolium; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester