| Summary: | 碩士 === 慈濟大學 === 醫學研究所 === 94 === The pattern of chronic intermittent hypoxia (CIH) is a characteristic of pathological conditions such as obstructive sleep apnea and is associated with serious cardiovascular morbidity. CIH produces the oscillation of arterial blood oxygen levels which are monitored continuously by peripheral chemoreceptors, especially the carotid bodies. CIH seems to resemble ischemia-reoxygenation, wherein reactive oxygen species (ROS) released during the intervening normoxic periods. Several evidences suggest that ROS may involved in the repeated carotid body stimulation under CIH, which led to chemoreflex and cardiovascular responses. However, the time course changes and ROS-dependent mechanisms in the chemoreflex and cardiovascular responses to CIH are not clear. In this study, we examined whether CIH (6 h/day, for 30 days) affects in chemoreflex and cardiovascular responses in conscious rats and, if so, determine whether superoxide anion and hydroxyl radical play a critical role in mediating these cardiorespiratory responses.
Adult male Sprague-Dawley rats were exposed to CIH (75 s/episode, 6 h/day, for 30 days) during sleep period. Blood pressure signals were measured daily by the telemetry system, which were used to assess the autonomic function by heart rate variability analysis. Ventilatory responses during room air (RA) breathing, an index for tonic chemoreflex activation, and 12% O2 (acute hypoxia) breathing, an index for phasic chemoreflex, were monitored daily. Mean arterial blood pressure (MABP) and normalized low-frequency power of pulses interval spectrogram (LF%), the marker of cardiac sympathetic outflow, were significantly higher in IH-exposed rats, as compared that of RA-exposed rats. Additionally, elevation of the MABP, LF%, and minute ventilation started 5-6 days after IH exposure and lasted until the end of the observation period. Pretreatment with MnTMPyP (a superoxide anion scavenger) prevented CIH-induced these responses and lipid peroxidation in lung tissue. In CIH-exposed rats pretreated with dimethylthiourea (DMTU; a hydroxyl radical scavenger), the enhanced minute ventilation was not significantly affected, whereas the elevated MABP and LF% were reduced. However, no significant difference in the metabolic rate were observed among groups. These results suggest that CIH-induced hypertension is associated with chemoreflex activation and facilitation of sympathetic outflow, and ROS plays an important role in CIH-induced these responses.
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