Cardiac Neural Regulation Oscillates with the Estrous Cycle in Freely Moving Female Rats: The Role of Endogenous Estrogens

Both estrogens levels and sleep/wakefulness states have been separately reported to affect cardiac autonomic regulation. In this study, we examined the integrated effects of the estrous and sleep cycles on cardiac autonomic activity in freely moving adult female rats. Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability. High-frequency power (HF) and low-frequency power to HF ratio are closely correlated with cardiac parasympathetic and sympathetic activity, respectively. Ten days after electrodes were implanted, electroencephalogram, electromyogram, and electrocardiogram were recorded 6 h daily for 12 consecutive days to cover at least two estrous cycles. Estrous-cycle stages were determined using vaginal smears. Sleep cycle-related heart rate variability parameter oscillations were seen in all rats. However, the estrous cyclicity and estrous-cycle-related changes were only observed in the control rats and not in ovariectomized or the estrogen receptor antagonist, tamoxifen, treatment rats. A significantly higher HF was observed in estrous rats compared with diestrous rats or ovariectomized rats no matter whether the rats were asleep or awake. However, a significantly low-frequency power to HF ratio was only observed in quiet sleep (QS) during estrus. All these differences disappeared after treatment with tamoxifen. Our results suggest that estrous-cycle-related changes in cardiac neural regulations can be mainly attributed to endogenous estrogens, and these effects are most obviously manifest during QS. Estrous rats during QS would be equivalent to the late follicular phase of the women menstrual cycle and involve strong vagal tone but weak sympathetic activity.