Sex Differences in Angiotensin Signaling in Bulbospinal Neurons in the Rat Rostral Ventrolateral Medulla

Gang Wang, Teresa A. Milner, Robert C. Speth, Andrea C. Gore, Di Wu, Costantino Iadecola, and Joseph P. Pierce

The risks for hypertension have long been studied, but more recently the differences in risks between sexes have started to be studied as it has been found that there is a significant difference between men and women. Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) control the regulation of blood pressure and are implicated in the development of hypertension. Specifically, angiotensin II and its receptor AT1 in the RVLM are implicated it the development of hypertension. In this study RVLM neurons were studied to evaluate the difference in AT1 receptors, subunit p47 of NAPDH oxidase and the effects of angiotensin II on reactive oxide species (ROS) production between male and female rats.

Sprague-Dawley rats were used in this study and all female rats received bilateral ovariectomies and then were given estrogen replacement, this was to take out the variability of all hormones that come with being a female and just examine the effect of estrogen. Female rats were then implanted with capsules containing estradiol or a 100% cholesterol vehicle. In this study antibodies were used to assess the level of expression of the parameters described above. After rats were sacrificed coronal sections of the brain were taken and antibody labeling of AT1 and the p47 subunit was done. A certain population of cells was also exposed to angiotensin II and then the level of intracellular reactive oxygen species was measured.

This study found that there is more AT1 in females than in the males. Similarly, it was found that the females that were ovariectomized and given estrogen had more AT1 than the females that were ovariectomized and not given estrogen. Females also contained lower levels of p47 subunits that the males. ROS production after administration of angiotensin II did not differ between male and female rats, although it was found that the L-type calcium currents induced by angiotensin II were significantly larger in the females compared to the males.

This study shows that estrogen, which is the major hormone in females, can modulate differences in properties of the RVLM and that these differences can contribute to molecular mechanisms that are linked to hypertension. This was interesting because it shows that there are many differences between the male and female brain and that there is a lot to explore along this line of thinking. It is already known that there is a major difference in the development of hypertension between men and women, the mechanisms behind this may be related to hormones, but there is still that is unknown.

Ben R