Summary:We investigated the alterations in the stable end products of nitric oxide, i.e., nitrate and nitrite, in the plasma during and after rat focal cerebral ischemia by an automated procedure based on the Griess reaction. At 2 h of middle cerebral artery (MCA) occlusion, plasma ni trate/nitrite levels were significantly higher (53 ± 8 ILM, mean ± SD, n = 5, p < 0.05) than in rats with sham operation (36 ± 9 ILM, n = 5), and were mildly elevated at 4 h of MCA occlusion (42 ± 9 ILM, n = 5, n.s.). At 30 min of reperfusion after 2 h of MCA occlusion, plasma nitrate/nitrite levels were more markedly elevated (72 ± 7 ILM, n = 5, p < 0.01 vs. sham operation), but were mod erately elevated at 2 h of reperfusion after 2 h of MCA occlusion (61 ± 10 ILM, n = 5, p < 0.05). Plasma nitrite To date, nitric oxide is considered both a free rad ical, an endothelium-derived relaxing factor, and a neurotransmitter (Palmer et aI., 1987;Garthwaite, 1991). In view of the fact that NOS is distributed within the brain, nitric oxide could be deeply in volved in the pathophysiology of cerebral ischemia Received July 9, 1993; final revision received September 7, 1993; accepted October 6, 1993.Address correspondence and reprint requests to Dr. Eiji Ku mura, Department of Physiology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.Abbreviations used: ANOVA, analysis of variance; L-NAME, �-nitro-L-arginine methyl ester; MeA, middle cerebral artery; NOS, nitric oxide synthase. 487 levels were not changed during these experimental peri ods. Administration of 20 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME) significantly decreased plasma nitrate/nitrite as well as nitrite at 30 min of reperfusion after 2 h of MCA occlusion (n = 5), but 2 mg/kg of L-NAME did not (n = 3). The effect of 20 mg/kg of L-NAME on plasma nitric oxide end products was re versed by the simultaneous administration of 200 mg/kg of L-arginine (n = 3), but not D-arginine (n = 3). The present study suggests that the L-arginine-nitric oxide pathway is activated during acute cerebral ischemia and reperfusion.