Cárdenas A, De Alba J, Moro M A, Leza J C, Lorenzo P, Lizasoain I
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Eur J Pharmacol. 1998 Aug 7;354(2-3):161-5. doi: 10.1016/s0014-2999(98)00458-0.
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.
有人提出，诱导型一氧化氮合酶产生的大量一氧化氮（NO）参与了脑缺血后的神经毒性机制。我们最近证明，大鼠前脑切片暴露于氧糖剥夺后数小时内诱导型一氧化氮合酶就会表达。因此，我们试图通过使用一种新型、高选择性的诱导型一氧化氮合酶抑制剂N-(3-(氨甲基)苄基)乙脒（1400W）来确定诱导型一氧化氮合酶产生的NO是否会导致该模型中的组织损伤。我们发现，从氧糖剥夺期开始到实验结束，用1400W孵育可减少在氧糖剥夺期4小时后测定的组织损伤，以乳酸脱氢酶（LDH）流出量表示，在该模型中此时诱导型一氧化氮合酶的表达最高。这种作用可能是直接抑制诱导型一氧化氮合酶活性的结果，这增加了在脑缺血治疗中临床使用这种一氧化氮合酶同工型选择性抑制剂的可能性。
