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 o xide, i.e., nitrate and nitrite, in the plasma during and after rat fo cal cerebral ischemia by an automated procedure based on the Griess re action. At 2 h of middle cerebral artery (MCA) occlusion, plasma nitra te/nitrite levels were significantly higher (53 +/- 8 mu M, mean +/- S D, 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, p lasma nitrate/nitrite levels were more markedly elevated (72 +/- 7 mu M, n = 5, p < 0.01 vs. sham operation), but were moderately elevated a t 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 exper imental periods. Administration of 20 mg/kg of N-G-nitro-L-arginine me thyl 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 o f L-NAME on plasma nitric oxide end products was reversed by the simul taneous administration of 200 mg/kg of L-arginine (n = 3), but not D-a rginine (n = 3). The present study suggests that the L-arginine-nitric oxide pathway is activated during acute cerebral ischemia and reperfu sion.