Orlando G F, Langnaese K, Landgraf R, Spina M G, Wolf G, Engelmann M
Institute of Medical Neurobiology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Nitric Oxide. 2007 Feb;16(1):64-70. doi: 10.1016/j.niox.2006.05.002.
This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.
本研究旨在探讨在基础条件下以及对强迫游泳的反应中，一氧化氮合酶（nNOS）的神经亚型所产生的一氧化氮（NO）对神经型一氧化氮合酶基因敲除（KO）小鼠和野生型（WT）小鼠下丘脑神经垂体系统活性的重要性。与野生型小鼠相比，基因敲除小鼠下丘脑视上核（SON）中抗利尿激素（AVP）的杂交信号强度显著更高，而两组中催产素（OXT）的基础mRNA水平相似。尽管两种基因型小鼠中AVP和OXT的基础外周释放量相当，但我们观察到，在基因敲除小鼠中，应激源开始作用15分钟后，AVP和OXT的血浆值显著下降，而在60分钟时，OXT血浆浓度大幅升高。这些发现表明，在雄性小鼠中，NO抑制视上核大细胞神经元中AVP基因的转录，并在急性应激源暴露后协同维持AVP和OXT血浆水平的恒定，对OXT分泌发挥双峰调节作用。我们得出结论，NO参与视上核大细胞神经元的调节，并且它优先参与减弱急性应激源暴露所诱导的OXT外周释放。
