Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairments

De Melo VU, Saldanha RRM, Dos Santos CR, et al. Ovarian Hormone Deprivation Reduces Oxytocin Expression in Paraventricular Nucleus Preautonomic Neurons and Correlates with Baroreflex Impairment in Rats. Frontiers in Physiology. 2016;7:461. doi:10.3389/fphys.2016.00461.

              Some studies have shown that the incidence of cardiovascular disease in women increases as they go through menopause. The exact mechanisms for this are unclear and need to be further investigated. It has been suggested that it is due to the decrease in estrogen levels in the women’s body. Specifically hypertension is one of the diseases cited that has a dramatic increase after women go through menopause. Some neurons in the paraventricular nucleus of the hypothalamus (PVN) utilize oxytocin as a neurotransmitter and project to the brainstem and are involved in the regulation of the cardiovascular system via sympathetic outflow. These PVN neurons express estrogen receptors. The current study hypothesizes that estrogen binds to these neurons and increases their outflow to the brainstem thus increasing sympathetic outflow, and that if estrogen deprived this system would be dysregulated and could cause hypertension. They also state that the increase in cardiovascular ability is due to the increase in baroreceptor sensitivity and that without estrogen that is impaired.

              The current study used 33 female Wistar rats that were kept on a 12:12 light dark cycle. These were randomly divided into two groups, one that was ovariectomized (OVX) and one that had a sham surgery. OVX group was used as the group with no circulating estrogen that would be binding in the PVN. Surgeries were performed at 10 weeks of age. After 8 more weeks, rats were implanted with catheter and cardiovascular parameters were measured. At this time spontaneous baroreflex sensitivity was measured as well. Brain slices were obtained from the rats after they were sacrificed and PCR analysis of mRNA expression as well as oxytocin expression was analyzed.

              It was found that the OVX rats weighed more at the end of the study, and that they had a higher resting mean arterial pressure as well as a higher heart rate. In some nuclei of the PVN it was found that oxytocin mRNA and protein expression levels were significantly lower in the OVX rats as compared to the sham surgery rats. In these rats where there was less oxytocin expression, there was a strong correlation with decreased autonomic control as measured by baroreflex sensitivity. This study provides support for the idea that without the estrogen hormone, the baroreceptor reflex is impaired which causes dysregulation of the sympathetic system and possibly increases in blood pressure. It is shown in this study that reduced oxytocin expression in the PVN neurons may be one of the molecular mechanisms behind this increase in blood pressure after hormone deprivation.

              I think the findings from this study are interesting in light of us trying to initiate ovariectomy experiments in rats within our own laboratory. The findings are interesting and give a potential mechanism for the reason that estrogen has a protective cardiovascular effect. This study mainly focuses on the PVN neurons that express estrogen receptors and are oxytogenic in nature, however it is these neurons that modulate activity in the rostral ventrolateral medulla, the focus in this lab.

Ben R - blog alter ego TBD