Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.
Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.
复制标题
一氧化氮合酶抑制可减少猫短暂局灶性缺血后的尾状核损伤。
DOI：
10.1161/01.str.25.4.877
复制
发表时间：
1994
期刊：
影响因子：
8.3
通讯作者：
Traystman,RJ
中科院分区：
文献类型：
--
作者：
Nishikawa,T;Kirsch,JR;Koehler,RC;Miyabe,M;Traystman,RJ
我们验证了在短暂性局灶性脑缺血之前或期间抑制一氧化氮产生影响缺血后早期脑损伤的假设。氟烷麻醉的猫进行了左侧大脑中动脉闭塞1小时加再灌流3小时。预处理组于缺血前30min静脉注射N-奥米伽-硝基-L-精氨酸甲酯(L-NAME，10 mg/kg，n=10)或等体积稀释液(生理盐水10mL，n=10)。后处理组在缺血45min至再灌流15min的30min内静脉注射L-NAME(10 mg/kg)，或在此期间静脉注射L-NAME(10 mg/kg)+L精氨酸(200 mg/kg)，然后继续静脉滴注L-精氨酸(200 mg/kg/h)以维持再灌注(n=10)。4组大鼠缺血时同侧尾状核和颞叶下皮质微球测定的血流量均有不同程度的下降，再灌流时均有相同程度的恢复。用三苯基四氮唑测定缺血前和缺血时L-NAME组猫同侧尾状核损伤体积(分别占尾状核的42+/-7%和42+/-3%；平均+/-SE)小于生理盐水组(72+/-5%)和L-NAME+L-精氨酸组(68+/-5%)(P<；0.05)。4组同侧大脑半球损伤体积相似(缺血前、缺血期间给予L-NAME组分别为23+/-5%、13+/-3%、18+/-5%、29+/-5%，生理盐水组和L-NAME+L-精氨酸组分别为23+/-5%、13+/-3%、18+/-5%、29+/-5%)。抑制一氧化氮合酶可减少猫短暂性局灶性脑缺血后尾状核损伤体积。这种有益作用被L-精氨酸逆转，并不是由于缺血和再灌流过程中血流的良好重新分配所致。因为L-NAME在再灌流时是有效的，再灌流期间产生的一氧化氮似乎参与了尾状核损伤。
We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury.Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n = 10) over 30 minutes before ischemia. Posttreatment groups received intravenous L-NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg) over the same period followed by continuous L-arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n = 10).Microsphere-determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and during ischemia, the saline-treated group, and the group treated with L-NAME plus L-arginine, respectively).Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by L-arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury.