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 -

急性进行性缺氧对清醒大鼠心率和血压变异的影响 - 纹状体自主神经活动和细胞外多巴胺水平的评估 -

• 批准号: 15592106
• 负责人: SUGIMURA Mitsutaka
• 金额: $ 2.37万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592106/
• 关键词: hypoxia; autonomic nerve; sympathetic nerve activity; parasympathetic nerve activity; blood pressure variability; heart rate variability; dopamine; serotonin; 交感神経系活性; 心臓迷走神経系活性

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

本研究旨在探讨急性进行性低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。我们从动脉血压和心率分析每个变异性，以评估自主神经反应。由于功率谱具有较高的时间分辨率，我们采用小波方法进行功率谱分析。雄性自发性高血压大鼠(SHR280~330g，12周龄)，参照Paxinos和Watson图谱[A+0.2 mm，L+2.8 mm，V+3.4 mm]，经股动脉插管测量血压，将微透析探头插入纹状体测量DA水平。在密闭的丙烯酸室中，在自由活动清醒状态下测量收缩压(SBP)、心率(HR)和多巴胺(DA)水平。在丙烯酸室中进行180min的对照测量后，给予含有20%氧气和80%氮气的混合气体，将大鼠暴露在…中更进行性的低氧状态。舱内氧气浓度在5分钟内降至F_1O_2=0.1(下降阶段)，并维持在F_1O_2=0.1的状态10分钟(固定阶段)。之后，在5分钟内(上升期和恢复期)恢复到F1O2=0.2。分别在下降(F_1O_2=0.15)、固定(F_1O_2=0.1)、上升(F_1O_2=0.15)、恢复期(F_1O_2=0.2)等6个时间点采样，并与对照组进行比较。以Wistar京都大鼠(WKY)为对照组。用大鼠自主神经分析软件(FLuclet^&lt；TM&gt；，Dainippon PharmicalCo.，小波方法)分析SBP波动的低频(SBP-LF；频率区0.25~0.75 Hz)和心率波动的高频(HR-HF；频率区0.75~3.0 Hz)。已知SBP-LF和HR-HF分别具有交感神经和副交感神经活动。统计分析采用SPSS统计软件。用双向重复测量方差分析和配对t检验评价低氧对这些变量的影响。采用Dunnett方法进行多重比较。数据以平均值±SE表示。P&lt；0.05在所有统计分析中均被认为是显著的。在SHR和WKY中，急性进行性低氧在所有阶段都表现为心动过速，而SBP在固定阶段表现为一过性升高。特别是SHR的血流动力学随着SBP-LF的加重和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进行性缺氧的下降和早期固定阶段交感神经活动的增强和副交感神经活动的减弱所致。但由于在SBP升高的情况下HR-HF的衰减仍保持不变，提示压力感受器反射敏感性随低氧的进行性减弱而减弱。此外，SHR的SBP在稳定期和升高期持续下降。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水平的升高均跟随SBP-LF的升高，滞后时间为10~15min，且表现出可逆性。较少