ELEVATION OF PLASMA NITRIC-OXIDE END-PRODUCTS DURING FOCAL CEREBRAL-ISCHEMIA AND REPERFUSION IN THE RAT

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 nitrate/nitrite levels were significantly higher (53 +/- 8 mu M, mean +/- SD, n = 5, p < 0.05) than in rats with sham operation (36 +/- 9 mu M, n = 5), and were mildly elevated at 4 h of MCA occlusion (42 +/- 9 mu M, 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 mu M, n = 5, p < 0.01 vs. sham operation), but were moderately elevated at 2 h of reperfusion after 2 h of MCA occlusion (61 +/- 10 mu M, n = 5, p < 0.05). Plasma nitrite levels were not changed during these experimental periods. Administration of 20 mg/kg of N-G-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 reversed 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.