The Influence of Acute Progressive Hypoxia on Heart Rate and Blood Pressure Variability in Awake Rats - The Evaluation of the Autonomic Nerve Activity and the extracellular dopamine level in the striatum -

本研究旨在探讨急性进行性缺氧对清醒大鼠自主神经系统活性和纹状体多巴胺（DA）水平的影响。我们分析了动脉血压和心率的每个变异性，以评估自主神经反应。由于功率谱分析具有时间分辨率高的特点，我们采用了小波分析方法。雄性自发性高血压大鼠（SHR, 280 ~ 330 g， 12周龄），根据Paxinos和Watson图谱[a +0.2 mm, L +2.8 mm, V +3.4 mm]，将导管插入股动脉测血压，微透析探针插入纹状体测DA水平。在意识自由活动状态下，在密闭的丙烯酸室内测量收缩压（SBP）、心率（HR）和DA水平。在给予含20%氧和80%氮的混合气体的丙烯酸腔中进行180分钟的对照测量后，大鼠暴露于更进行性缺氧状态。舱内氧浓度在5 min内（下降阶段）降至f_o_2 =0.1，并在f_o_2 =0.1维持10 min（固定阶段）。之后，在5 min内（上升和恢复阶段）恢复到f_10_2 =0.2。在下降（f_10_2 =0.15的交叉点）、固定（f_10_2 =0.1的交叉点后0,5和10 min的3个点）、上升（f_10_2 =0.15的交叉点）和恢复阶段（f_10_2 =0.2的交叉点）的6个点采样每个值，与控制值进行比较。以Wistar Kyoto大鼠（WKY）为对照组。采用大鼠自主神经分析软件（Fluclet^<TM>, DAINIPPON PHARMACEUTICAL CO.，LTD.）分析收缩压低频波动（SBP- lf，频率区0.25-0.75 Hz）和心率高频波动（HR- hf，频率区0.75-3.0 Hz）。（小波法）。已知SBP-LF和HR-HF分别表现交感神经和副交感神经活动。采用SPSS软件进行统计分析。通过双向重复测量方差分析和配对t检验评估缺氧对变量的影响。多重比较采用Dunnett法。数据以平均值±SE表示。P<0.05被认为是显著的。SHR和WKY均显示急性进行性缺氧在各阶段均诱发心动过速，在固定阶段均诱发短暂性收缩压升高。特别是SHR血流动力学随着SBP-LF的增强和HR-HF的减弱而发生显著变化。SHR的这些动态变化被认为是由于下降和早期固定阶段伴有进行性缺氧的交感神经活动增强和副交感神经活动减弱引起的。尽管收缩压升高，但HR-HF的衰减仍在持续，提示压力感受器反射敏感性随进行性缺氧而减弱。在固定后期和上升阶段，SHR的收缩压持续下降。推测这一系列变化主要是缺氧对心血管系统的直接作用所致。两组DA水平均随SBP-LF水平升高而升高，时间滞后10 ~ 15 min，且具有可逆性。少

The aim of this study is to examine the influence of acute progressive hypoxia on autonomic nervous system activity and dopamine (DA) level in the striatum in awake rat. We analyzed each variability from arterial blood pressure and heart rate for evaluating the autonomic response. We used power spectral analysis with wavelet method because of its high time resolution. Male spontaneous hypertensive rats (SHR, 280-330 g, the age of 12 weeks) were inserted a catheter into the femoral artery for measurement of blood pressure and the microdialysis probe into the striatum for that of DA level according to the atlas of Paxinos and Watson [A +0.2 mm, L +2.8 mm, V +3.4 mm from bregma]. Systolic blood pressure (SBP), heart rate (HR) and DA level were measured in an airtight acrylic chamber under freely moving conscious condition. After control measurements were taken for 180 min in the acrylic chamber, which was given the gas mixture contained 20% oxygen with 80% nitrogen, the rat was exposed in … More progressive hypoxic condition. Oxygen concentration in the chamber went down to F_1O_2=0.1 within 5 min (descent stage) and was maintained at F_1O_2=0.1 for 10 min (fixed stage). After that, it was returned to F_1O_2=0.2 within 5 min (ascent and recovery stages). Each value was sampled at 6 points during the descent (a crossing point of F_1O_2=0.15), the fixed (3 points of 0, 5 and 10 min after crossing point of F_1O_2=0.1), the ascent (a crossing point of F_1O_2=0.15) and recovery stages (a crossing point of F_1O_2=0.2) for comparison with the control value. Wistar Kyoto rats (WKY) were used as the control group. We analyzed low frequency of SBP fluctuation (SBP-LF ; frequency zone 0.25-0.75 Hz) and high frequency of HR fluctuation (HR-HF ; frequency zone 0.75-3.0 Hz) with the autonomic nerve analytical software for rat (Fluclet^<TM>, DAINIPPON PHARMACEUTICAL CO.,LTD., wavelet method). It has been known that SBP-LF and HR-HF show the sympathetic and parasympathetic activities, respectively. SPSS was used for the statistical analysis. The effects of hypoxia on the variables were evaluated by a two-way repeated-measures ANOVA and paired t test. The Dunnett method was used for multiple comparisons. Data are expressed as the mean±SE. P<0.05 was considered significant in all statistical analysis.It was exhibited in SHR and WKY that acute progressive hypoxia induced tachycardia during all stages and the transient increase in SBP during the fixed stages. In particular, hemodynamics in SHR changed markedly with the accentuation of SBP-LF and the attenuation of HR-HF. It was thought that these dynamic changes in SHR were caused by the accentuation of sympathetic activity and the attenuation of parasympathetic one during the descent and early fixed stages with progressive hypoxia. But because the attenuation of HR-HF was kept up in spite of the increase of SBP, it was suggested that the baroreceptor reflex sensitivity was weakening with progressive hypoxia. Moreover SHR showed the continuous decrease in SBP during the late fixed and ascent stages. It was speculated that such a series of changes were mainly caused by the direct action of hypoxia to the cardiovascular system. The increases in DA levels in both groups followed ones in the SBP-LF with the time lag of 10 to 15 min and exhibited reversibility. Less