Pechánová Olga, Jendeková Lýdia, Kojsová Stanislava, Jagla Fedor
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic.
Behav Brain Res. 2006 Nov 1;174(1):160-6. doi: 10.1016/j.bbr.2006.07.021. Epub 2006 Aug 28.
We aimed to analyze whether hypertension and changes in nitric oxide (NO) generation are associated with alterations of locomotor activity in rats. Male Wistar rats treated with an inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) for 6 weeks, control Wistar rats, spontaneously hypertensive rats (SHR), and control Wistar Kyoto rats (WKY) aged 18 weeks were investigated. Locomotor activities were tested by the open field method. NO synthase activity (NOS), concentration of cGMP and conjugated dienes (CD) as well as protein expression of nuclear factor NF-kappaB were determined in the cerebral cortex, cerebellum and brainstem. NOS activity in the brain parts investigated was not changed in SHR in comparison with the normotensive WKY. L-NAME treatment resulted in the decreased NOS activity in comparison with Wistar rats. The concentration of CD and expression of NF-kappaB protein, markers of reactive oxygen species, were higher and the concentration of cGMP was lower in hypertensive animals and more pronounced in SHR as well. Thus, the concentration of NO in the brain parts of SHR might be lower than in the L-NAME treated rats. L-NAME treatment increased horizontal (by 28%) and vertical (by 80%) motor activity. Similarly, in SHR both locomotor activities were increased by 105% and 148%, respectively, in comparison with WKY. In conclusion, decreased level of NO was associated with increased locomotor activity indicating that in addition to genetic differences which may determine changes in locomotor activity in hypertensive rats, the role of a signalling pathway mediated by NO may be supposed.
我们旨在分析高血压以及一氧化氮(NO)生成的变化是否与大鼠运动活动的改变相关。对18周龄的雄性Wistar大鼠用一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯(L-NAME,40mg/kg/天)处理6周,同时研究对照Wistar大鼠、自发性高血压大鼠(SHR)和对照Wistar Kyoto大鼠(WKY)。通过旷场试验检测运动活动。测定大脑皮层、小脑和脑干中的一氧化氮合酶活性(NOS)、环磷酸鸟苷(cGMP)和共轭二烯(CD)浓度以及核因子NF-κB的蛋白表达。与血压正常的WKY相比,SHR中所研究脑区的NOS活性没有变化。与Wistar大鼠相比,L-NAME处理导致NOS活性降低。高血压动物中,作为活性氧标记物的CD浓度和NF-κB蛋白表达更高,cGMP浓度更低,且在SHR中更明显。因此,SHR脑区中的NO浓度可能低于L-NAME处理的大鼠。L-NAME处理使水平运动活动增加(28%),垂直运动活动增加(80%)。同样,与WKY相比,SHR的两种运动活动分别增加了105%和148%。总之,NO水平降低与运动活动增加相关,这表明除了可能决定高血压大鼠运动活动变化的遗传差异外,还可能存在由NO介导的信号通路的作用。