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 -

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15592106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Osaka University
• Principal Investigator: SUGIMURA Mitsutaka Osaka University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (90244954)
• Co-Investigator(Kenkyū-buntansha): NIWA Hitoshi Osaka University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (30218250)
• Project Period (FY): 2003 – 2004
• Keywords: hypoxia / autonomic nerve / sympathetic nerve activity / parasympathetic nerve activity / blood pressure variability / heart rate variability / dopamine / serotonin

Research Abstract

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 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.