Differential nitric oxide synthase activity, cofactor availability and cGMP accumulation in the central nervous system during anaesthesia
Differential nitric oxide synthase activity, cofactor availability and cGMP accumulation in the central nervous system during anaesthesia
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DOI：
10.1093/bja/86.3.388
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发表时间：
2001-03-01
影响因子：
9.8
通讯作者：
Webster, NR
中科院分区：
文献类型：
--
作者：
Galley, HF;Le Cras, AE;Webster, NR
我们研究了麻醉对大鼠中枢神经系统（CNS）中一氧化氮（NO）产生、四氢生物蝶呤（tetrahydrobiopterin）浓度和环鸟苷酸（cGMP）积累的影响。将大鼠分配至氟烷、异氟烷、戊巴比妥、地西泮、氯胺酮或氙麻醉（每组n=6）。30 min后，将[C-14] L-精氨酸（i. v.）并且在另外60分钟的麻醉后，杀死大鼠并立即暴露于聚焦微波辐射。在切除大脑和脊髓后。放射性标记精氨酸产生的一氧化氮，以及麻醉期间的一氧化氮合酶活性）通过闪烁计数以[C-14] L-瓜氨酸的形式测定。cGMP测定酶免疫法和四氢生物蝶呤荧光HPLC法，在大脑区域和脊髓。一氧化氮合酶活性在所有脑区相似，但在脊髓较低，并不受麻醉。cGMP在中枢神经系统的所有区域中是相似的，并且在用氟烷麻醉的大鼠中显著降低。异氟烷产生类似的作用。相反，氯胺酮和氙麻醉增加cGMP在脊髓，脑干和海马。地西泮和戊巴比妥没有效果。四氢生物蝶呤浓度在中枢神经系统的所有领域是相似的，并增加在麻醉后的皮质和海马。我们已经证明了麻醉对大鼠中枢神经系统一氧化氮通路的深刻差异效应。
We investigated the effects of anaesthesia on dynamic nitric oxide production, concentrations of tetrahydrobiopterin and the accumulation of cyclic GMP (cGMP) in the rat central nervous system (CNS). Rats were assigned to anaesthesia with halothane, isoflurane, pentobarbital, diazepam, ketamine or xenon (n=6 per group). After 30 min, [C-14]L-arginine (i.v.) was given and, after a further 60 min of anaesthesia, rats were killed and exposed immediately to focused microwave radiation. After removal of the brain and spinal cord. nitric oxide production from radiolabelled arginine land hence nitric oxide synthase activity during anaesthesia) was measured as [C-14]L-citrulline by scintillation counting. cGMP was determined by enzyme immunoassay and tetrahydrobiopterin by fluorescence HPLC, in brain regions and the spinal cord. Nitric oxide synthase activity was similar in all brain regions but was lower in the spinal cord, and was unaffected by anaesthesia. cGMP was similar in all areas of the CNS and was significantly decreased in rats anaesthetized with halothane. Isoflurane produced similar effects. In contrast, ketamine and xenon anaesthesia increased cGMP in the spinal cord, brainstem and hippocampus. Diazepam and pentobarbital had no effect. Tetrahydrobiopterin concentrations were similar in all areas of the CNS and were increased in the cortex and hippocampus after anaesthesia. We have shown profound differential effects of anaesthesia on the nitric oxide pathway in the rat CNS.