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The overactive orexin system may play an important role in the poor sleep quality and its associated cardiorespiratory changes in neurogenic hypertension in Spontaneously Hypertensive Rats
Author(s) -
Briggs Logan,
Muggler Corey,
Li Aihua
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1235.4
Subject(s) - medicine , endocrinology , blood pressure , orexin , wakefulness , cardiorespiratory fitness , baroreflex , sleep (system call) , heart rate , receptor , neuropeptide , electroencephalography , psychiatry , computer science , operating system
Non‐dipper essential hypertensive patients suffer from sleep disturbances marked by many microarousal‐associated increases in blood pressure (BP), and the offspring of non‐dipper hypertension parents also showed a greater number of microarousals compared to the offspring of dipper hypertensive and normotensive control parents. Sleep disorders are closely linked to hypertension, and autonomic dysfunction, specifically altered chemoreflex control of sympathetic activity, may play a prominent role in this relationship. It has been reported that spontaneously hypertensive rats (SHRs) have higher sympathetic activity, elevated central and peripheral chemoreflexes, an impaired baroreflex, and poorer sleep quality. Recent studies have linked the orexin system to neurogenic hypertension in SHRs and showed that: 1) blocking orexin receptors with a dual orexin receptor antagonist can significantly lower BP in SHRs with no effect on BP in normotensive rats, and 2) SHRs have more orexin neurons in the lateral hypothalamus than that of normotensive WKY rats. In this study we ask: 1) are there age‐related sleep disturbances and associated cardiorespiratory changes in wakefulness and sleep in SHRs, and 2) will blocking orexin receptors improve the sleep quality and sleep‐associated cardiorespiratory disturbances in SHRs. SHRs at two ages, young (P28–45), and adult (3‐month), were used in this study. All the rats were instrumented with blood pressure telemeter, EEG and EMG electrodes, and 24hr blood pressure, heart rate and sleep‐wake cycle were recorded and analyzed. The results showed: 1) during the light period, SHRs spent 45% & 46% more time in wakefulness, 27% & 23% less time in NREM and 46% & 48% less time in REM sleep at young and adult age respectively compared to age‐matched normotensive WKY controls rats; 2) SHRs, both young and adult, have significantly decreased circadian‐related sleep‐wake and blood pressure difference; 3) SHRs have more sleep disturbance, microarousals and associated increases in BP than normotensive WKY control rats; 4) young SHRs appeared to spend more time in wakefulness than adult SHR during the light period (P=0.009); 5) blocking orexin receptor with a dual orexin receptor antagonist can significantly increase the time spend in sleep in both light and dark periods. In conclusion, SHRs have poor sleep quality from a very young age, and this may contribute to the progressive of hypertension. We suggest that the poor sleep quality in SHRs is associated with the overactive orexin system, and modulation of orexin system may be beneficial for improving sleep quality and treating hypertension in neurogenic hypertension. Support or Funding Information Dartmouth Undergraduate Research Office/ Howard Hughes Medical Institute for Undergraduate Research; NIH HL 28066.