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 -

本研究旨在观察急性进行性缺氧对清醒大鼠自主神经系统活动和纹状体多巴胺（DA）水平的影响。我们分析了动脉血压和心率的每个变异性，以评估自主反应。利用小波变换的高时间分辨率，采用功率谱分析方法。雄性自发性高血压大鼠（SHR，280-330 g，12周龄），按Paxinos和沃森图谱[A +0.2 mm，L +2.8 mm，V +3.4 mm]，股动脉插管测血压，纹状体微透析探针测DA。在清醒状态下，于密闭的丙烯酸室中测量收缩压（SBP）、心率（HR）和多巴胺（DA）水平。在给予含有20%氧气和80%氮气的气体混合物的丙烯酸室中进行180分钟的对照测量后，将大鼠暴露于 关于我们 进行性缺氧状态舱内氧气浓度在5 min内下降至F_1O_2=0.1（下降阶段），并在F_1O_2=0.1下维持10 min（固定阶段）。然后在5 min内恢复到F_1O_2=0.2（上升和恢复阶段）。在下降阶段（F_1O_2=0.15的交叉点）、固定阶段（F_1O_2=0.1的交叉点后0、5和10 min的3个点）、上升阶段（F_1O_2=0.15的交叉点）和恢复阶段（F_1O_2=0.2的交叉点）的6个点上采集每个值，以与对照值进行比较。Wistar京都大鼠（WKY）作为对照组。我们用大鼠自主神经分析软件（Fluclet<TM>，DAINIPPON PHARMACEUTICAL CO.，有限公司、小波方法）。已知SBP-LF和HR-HF分别显示交感神经和副交感神经活动。采用SPSS软件进行统计学分析。缺氧对各变量的影响采用双因素重复测量方差分析和配对t检验。使用Dunnett方法进行多重比较。数据表示为平均值±SE。SHR和WKY大鼠在急性进行性缺氧的各个阶段均出现心动过速，在固定阶段出现收缩压一过性升高。尤其是SHR的血流动力学变化明显，SBP-LF加重，HR-HF减弱。认为SHR的这些动态变化是由于在下降期和固定期早期，随着缺氧的进行，交感神经活动增强，副交感神经活动减弱所致。但随着SBP的升高，HR-HF的衰减仍在持续，提示随着缺氧的进行，压力感受器反射敏感性逐渐减弱。此外，SHR的收缩压在后期的固定和上升阶段持续下降。推测这一系列变化主要是由于缺氧对心血管系统的直接作用所致。两组DA水平的升高均随SBP-LF的升高而升高，但时间滞后10 ~ 15 min，且呈可逆性。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