The protective role of nitric oxide in the brain ischemia.
A role of nitric oxide in ischemia/reperfusion (I/R) injury of brain in normotensive (Sprague-Dowley rats, SD) and stroke-prone spontaneously hypertensive rats (SHR-SP) was studied. Cerebral ischemia was produced in rats by occlusion of the middle cerebral artery (MCA). NO and O2- releases in the brain in response to MCA occlusion followed by reperfusion were simultaneously monitored (2h) using electrochemical microsensors. The size of infarct was evaluated in the course of I/R from images of brain slices stained with 2,3,5-triphenyltetrazolium chloride. Similar patterns of NO and O2- releases were exhibited for SD and SHR-SP rats in the entire course of the experiments. However, the concentration of NO release was significantly lower during I/R in SHR-SP than in SD rats (the maximal NO concentration was 2.61 +/- 0.22 micromol/L for SD and 1.51 +/- 0.16 micromol/L for SHR-SP rats; *P < 0.01). In contrast, the concentration of O2- release during cerebral ischemia was significantly higher in SHR-SP than SD rats (the maximal increase was 122 +/- 24 nmol/L for SD and 220 +/- 44 nmol/L for SHR-SP rats; *P<0.01). The infarct sizes revealed in the course of I/R were larger in SHR-SP than SD rats (1.8 +/- 0.4% vs. 1.1 +/- 0.4% at 30 min., 2.84 +/- 0.8% vs. 2.21 +/- 0.6% at 100 min. and 9.20 +/- 1.1% vs. 5.8 +/- 0.6% at 180 min. ofthe brain weights, respectively; *P < 0.01 for each time-point). These studies indicate that nitric oxide plays a protective role during I/R and deficiency of NO in SHR-SP rats is due to excess of O2- production. The deficiency in NO concentration correlates positively with the increase of cerebral I/R injury.
Dobrucki
L W
LW
Department of Chemistry and Biochemistry, Ohio University, Athens 4570-2979, USA.
Kalinowski
L
L
Uracz
W
W
Malinski
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013481:Superoxides / Q000378:metabolism
D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide