| Effects of Nitric Oxide Synthase Inhibition on Hydroxyl Radical Production during Global Cerebral Ischemia/Reperfusion in Rats. |
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So Young Lim, Jin Soo Kim, Wan Soo Oh, Kwang Min Kim |
1Department of Anesthesiology, College of Medicine, Hallym University.
2Pundang Jesaeng General Hospital. |
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| Abstract |
BACKGROUND
Free radical-mediated oxidative damage has been implicated in ischemic brain injury. There are also increasing evidences that nitric oxide is involved in the mechanisms of cerebral ischemia. To elucidate the effect of nitric oxide synthesis inhibition on the hydroxyl radical formation, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3-DHBA following salicylate adminstration.
METHODS
Sprague-Dawley rats were subjected to 15 min of global cerebral ischemia by both carotid artery occlusion plus systemic hemorrhagic hypotension (35 mmHg). Artificial CSF including salicylate (5 mM) was continuously infused through a microdiaysis probe implanted in the left hippocampus CA1. Hippocampal extracellular fluid was sampled at regular intervals before, during, and after ischemia. The levels of 2,3-DHBA were assayed by HPLC with electrochemical detection during 15 minutes of ischemia and reperfusion period.
RESULTS
Cerebral blood flow was reduced to 5% level of control in ischemic period, but increased 3 or 4 times in early phase of reperfusion period, and returned to normal 50 to 60 minutes after the cessation of ischemia. Inhibition of NOS by L-NAME did not prevent ischemia-induced 2,3-DHBA elevation, but increased its level during reperfusion. This increase in 2,3-DHBA could be reversed by L-arginine. The elevated 2,3-DHBA after IR in L-NAME treated rats was not due to either changes in CBF or local blood brain barrier permeability.
CONCLUSIONS
The above results indicate NO protects brain from damages by hydroxyl radical, at least less than one hour after initiation of reperfusion. |
| Key Words:
Brain, global ischemia, reperfusion; Equipment, high performance liquid chromatography, microdialysis; Pharmacology, hydroxyl radical, nitric oxide synthase inhibitor |
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