EFFECT OF N-NITRO-L-ARGININE METHYL-ESTER (L-NAME) ON REGIONAL CEREBRAL BLOOD-FLOW IN A MODEL OF FOCAL ISCHEMIA OF MIDDLE CEREBRAL-ARTERY IN RAT

We investigated the influence of L-NAME, a nitric oxide synthase (NOS) inhibitor, on regional cerebral blood flow (CBF) in the rat focal ischemic brain. An ischemic lesion was created by the direct obliteration of the left middle cerebral artery (MCA). CBF was measured by using a hydrogen gas tissue blood flow meter at the ischemic penumbra and at its contralateral symmetrical site. Within 15 min of the occlusion, L-NAME (1.5 mg/kg/min for 45 min, n = 10 or 30 mg/kg for 45 min, n = 5) was infused intravenously to the experimental group and normal saline was given to the control group (n = 6) for 45 min. In the two L-NAME groups, mean CBF on the left side was reduced to 44.1 and 37.4%, respectively, after MCA occlusion, as compared with initial CBF, and further decreased to 29.6 and 29.3%, respectively, after administration of L-NAME. CBF at the contralateral site in the two L-NAME groups was 99.1 and 86.9%, respectively, of initial CBF after MCA occlusion, then fell significantly to 80.9 and 58.5%, respectively, after administration of L-NAME. Results indicated that L-NAME reduced CBF at the ischemic penumbra as well as at the non-ischemic contralateral cerebral cortex. We also estimated the size of the infarcted area in three rats in the L-NAME-treated group by TTC stain, and compared the values with those of five rats in the control group. While the mean infarct ratio of L-NAME-treated rats (49.97%) was smaller than that of control rats (57.78%). The diference was not statistically significant: We conclude that L-NAME reduced CBF to the ischemic penumbra as well as to the non-ischemic contralateral region. Deta thus suggest that L-NAME to reduced the size of the infarcted area.