Ayers N A, Kapás L, Krueger J M
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Neurochem Res. 1997 Jan;22(1):81-6. doi: 10.1023/a:1027385522859.
We studied the effects of intracerebroventricular and intraperitoneal injection and the in vitro effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the nitric oxide synthase activities of the cerebellum, brainstem, hypothalamus, hippocampus, and the remainder of the brain after dissections. Male rats were chronically implanted with lateral icv guide cannula. L-NAME was injected in doses of 0.2, 1, and 5 mg intracerebroventricularly, and 50 mg/kg intraperitoneally. L-NAME induced dose-dependent suppression of NOS activities in each brain region. The threshold dose was 0.2 mg; 1 mg L-NAME completely abolished brain nitric oxide synthase activity 90 min after the injection. Brain NOS activities returned to baseline level 48 h after the injection of 5 mg L-NAME. There were significant differences between the sensitivity of various regions to L-NAME after in vivo but not in vitro administration of the enzyme inhibitor. These findings indicate that intracerebroventricular injection of L-NAME is a useful tool for inhibiting brain nitric oxide synthase activities in vivo. The differences between the sensitivity of different brain regions to L-NAME as well as the relative fast recovery of nitric oxide synthase activities must be taken into account when L-NAME is administered intracerebroventricularly to rats.
我们研究了脑室内和腹腔内注射一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）的效果，以及其对解剖后的小脑、脑干、下丘脑、海马体和大脑其余部分一氧化氮合酶活性的体外影响。雄性大鼠长期植入侧脑室引导套管。L-NAME以0.2、1和5毫克的剂量进行脑室内注射，以及50毫克/千克的剂量进行腹腔内注射。L-NAME诱导了每个脑区一氧化氮合酶活性的剂量依赖性抑制。阈值剂量为0.2毫克；注射1毫克L-NAME后90分钟，脑一氧化氮合酶活性完全被消除。注射5毫克L-NAME后48小时，脑一氧化氮合酶活性恢复到基线水平。在体内而非体外给予酶抑制剂后，不同脑区对L-NAME的敏感性存在显著差异。这些发现表明，脑室内注射L-NAME是体内抑制脑一氧化氮合酶活性的有用工具。当向大鼠脑室内注射L-NAME时，必须考虑不同脑区对L-NAME敏感性的差异以及一氧化氮合酶活性相对较快的恢复情况。
