Rat model for exploring the possible roles of cardiovascular neural regulation on late sleep-related higher cardiovascular events

• Main Authors: Chun-Ting Lai, 賴俊廷
• Other Authors: Cheryl C.H. Yang
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/21691358828057545270

博士 === 國立陽明大學 === 腦科學研究所 === 104 === Background Many epidemiological studies have report the risk of cardiovascular events is highest during the early morning and also associated with the sleep/wake transition. During this periods, the sleep become unstable and more fragmentation as well as the sympathetic hyperactivity and blood pressure surge. We propose the sleep-related cardiovascular regulation could have a critical role, and using the rat model to explore the mechanisms of the abnormal cardiovascular regulation during the late-sleep periods. In addition, the hypertensive patients and post-menopausal women also show more severe in risk of cardiovascular events that could associate with cardiovascular regulation. Methods Polysomnographic recording was performed through wireless transmission in freely moving rat over 24 hours. Continuous EEG, EMG, ECG and blood pressure signals were been use to analysis the sleep, heart rate variability (HRV), arterial blood pressure variability (ABP) and baroreflex sensitivity (BRS). Compare the difference between normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) in cardiovascular regulation during the late-light periods. And compare the difference between the ovariectomized (OVX) with or without estrogen supplement to explore role of estrogen in cardiovascular regulation during late-light periods. Results Firstly, as we compared with early-light period (Zeitgeber time 0-6 h), rats during the late-light period (Zeitgeber time 6-12 h) showed more sleep fragmentation, sympathetic activity, BRS impairment, and a significant correlation between sleep architecture and sympathetic activity during the light period of quiet sleep (QS) Secondly, we found the SHR have a significant blood pressure surge during late-light periods. According the definition in human, we defined that were a wake-related blood pressure surge, WBPS. During the late-light periods, the sympathetic indexes- low frequency percentage of heart rate variability (LF%) and low frequency of arterial blood pressure (BLF) have a significant associated with sleep indexes. Under 1-adrenergic antagonism, the late-light period related sleep fragmentation and BP surge were partially reversed. Thirdly, compared OVX+O and OVX-E, the OVX+E group showed the less sleep fragmentation and sympathetic surge. Estrogen could modulate and decrease the autonomic imbalance during the late-light sleep-related sympathetic and blood pressure surge. Conclusion We established the rat’s model to resemble the human late-sleep-related sympathovagal imbalance and blood pressure surge that may associated with the higher cardiovascular events. During the late-light periods, the rats showed sleep fragmentation, sympathetic hyperactivity, baroreflex impairment and WBPS, which results were exaggerated in SHRs. Under α1-adrenergic antagonism, the late-light period related sleep fragmentation and BP surge in the SHRs were partially reversed. The rat models were also used to explore the effects of estrogen no autonomic regulation during the late-light sleep. Our results provide some clues that should help the development of antihypertensive treatments and the treatments for the late-sleep-related problems.