Protective effect of N-(3-(aminomethyl benzyl) acetamidine, an inducible nitric oxide synthase inhibitor, in brain slices exposed to oxygen-glucose deprivation

被引:38
作者
Cárdenas, A [1 ]
De Alba, J [1 ]
Moro, MA [1 ]
Leza, JC [1 ]
Lorenzo, P [1 ]
Lizasoain, I [1 ]
机构
[1] Univ Complutense Madrid, Fac Med, Dept Farmacol, E-28040 Madrid, Spain
关键词
brain; forebrain slice; ischaemia; nitric oxide (NO) synthase; (rat); 1400W (N-(3-(aminomethyl)benzyl)acetamidine);
D O I
10.1016/S0014-2999(98)00458-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been suggested that large amounts of nitric oxide (NO) produced by inducible NO synthase are involved in the mechanisms of neurotoxicity after cerebral ischaemia. We have recently demonstrated that inducible NO synthase was expressed within hours after rat forebrain slices were exposed to oxygen-glucose deprivation. Therefore, we sought to determine whether NO produced by inducible NO synthase contributes to tissue damage in this model, by using a new, highly selective, inhibitor of inducible NO synthase, N-(3-(aminomethyl)benzyl)acetamidine (1400W). We found that incubation with 1400W from the start of the oxygen-glucose deprivation period until the end of the experiment decreases tissue damage determined as lactate dehydrogenase (LDH) efflux 4 h after the oxygen-glucose deprivation period, the time at which inducible NO synthase expression is maximal in this model. This effect may be a result of direct inhibition of inducible NO synthase activity, raising the possibility of a clinical use of selective inhibitors of this NO synthase isoform in the management of cerebral ischaemia. (C) 1998 Elsevier Science B.V. All rights reserved.
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页码:161 / 165
页数:5
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