Jiang Min Hai, Kaku Tomohiro, Hada Junichi, Hayashi Yasumasa
Department of Physiology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Brain Res. 2002 Aug 9;946(1):139-47. doi: 10.1016/s0006-8993(02)02870-6.
To clarify the functions of nitric oxide (NO) induced by either neuronal NO synthase (nNOS) or endothelial NO synthase (eNOS) after transient cerebral ischemia, we investigated the effects of L-N(5)-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, and 7-nitroindazole (7-NI), a relatively selective nNOS inhibitor, on hippocampal dysfunction caused by cerebral ischemia. We measured mean arterial blood pressure (MABP), hippocampal blood flow, direct current (DC) potential, CA1 population spike (PS) and extracellular concentrations of glutamate from rat hippocampus after transient forebrain ischemia, which was induced by four-vessel occlusion for 10 min. L-NIO (20 mg/kg) and 7-NI (25 mg/kg) were administered intraperitoneally 20 min before ischemia. L-NIO, but not 7-NI, increased MABP before, during and after ischemia, compared with the vehicle group. 7-NI, but not L-NIO, reduced the amplitude of anoxic depolarization induced by ischemia. 7-NI recovered the PS amplitude in part 60 min after ischemia. 7-NI, but not L-NIO, reduced the ischemia-induced levels of glutamate. These results indicate that nNOS inhibition with 7-NI improves, at least in part, hippocampal dysfunction after ischemia, while eNOS inhibition with L-NIO worsens it.
为阐明短暂性脑缺血后神经元型一氧化氮合酶（nNOS）或内皮型一氧化氮合酶（eNOS）所诱导的一氧化氮（NO）的功能，我们研究了相对选择性的eNOS抑制剂L-N(5)-(1-亚氨基乙基)鸟氨酸（L-NIO）和相对选择性的nNOS抑制剂7-硝基吲唑（7-NI）对脑缺血所致海马功能障碍的影响。我们测量了四动脉闭塞10分钟诱导的大鼠前脑短暂性缺血后平均动脉血压（MABP）、海马血流量、直流电（DC）电位、CA1群体峰电位（PS）以及大鼠海马谷氨酸细胞外浓度。在缺血前20分钟腹腔注射L-NIO（20毫克/千克）和7-NI（25毫克/千克）。与溶剂组相比，L-NIO而非7-NI在缺血前、缺血期间和缺血后均使MABP升高。7-NI而非L-NIO降低了缺血诱导的缺氧去极化幅度。7-NI在缺血后60分钟部分恢复了PS幅度。7-NI而非L-NIO降低了缺血诱导的谷氨酸水平。这些结果表明，用7-NI抑制nNOS至少部分改善了缺血后海马功能障碍，而用L-NIO抑制eNOS则使其恶化。
