Structural differences in aortic baroreceptors of male and female mice may contribute to sex differences in cardiovascular disease

Hypertension, or high blood pressure, is a major risk factor for cardiovascular disease, the leading cause of mortality worldwide. Hypertension affects men and women differently. Men have higher prevalence in middle age, whereas women have higher prevalence that exceeds men in older age. Thus, there is a need to understand mechanisms that contribute to sex-specific differences in hypertension. The homeostatic baroreflex maintains blood pressure at levels optimal for our survival. This achieved by aortic baroreceptors which monitor stretch at the aortic arch and convey these signals to the hindbrain, which in turn regulates blood pressure. We have previously developed a novel approach to selectively label and target aortic baroreceptors that innervate the aortic arch. Age-matched male and female C57BL/6J mice were anesthetized with isoflurane, intubated, and artificially ventilated. Following sternotomy, the aortic arch was exposed, and a retrograde adeno-associated virus was applied to the aortic arch to direct the expression of tdTomato (tdTom) in aortic baroreceptors. Consistent with the structural characteristics of aortic baroreceptors, robust tdTom expression was observed in nerve endings surrounding the aortic arch, within the fibers of the aortic depressor and vagus nerves, cell bodies within the nodose ganglion (NDG), and neural projections to the nucleus of the solitary tract (NTS). Interestingly, we found structural differences between male and female mice in the neuroanatomical circuit of aortic baroreceptors. Labeled aortic baroreceptors consisted of ~9% and 13% of total NDG neurons in male and female mice respectively. The number of tdTom labelled aortic baroreceptor neurons in the left and right nodose ganglion were also different between male and female mice (male; left: 110±9, right: 82±9, female; left:156±18, right:141±5 TdTom-labeled neurons). This indicates that females have a higher number of aortic baroreceptors residing in the NDG than in male mice. Next, we analyzed the densities of nerve ending innervating the aortic arch and fiber projections to the NTS. Our preliminary data suggest differences between male and female mice in innervating and projecting nerve endings. Collectively, our data indicates a difference between males and females in the anatomical structure and innervation pattern of aortic baroreceptors. These structural differences may contribute to sex differences in the regulation of blood pressure and cardiovascular disease. Funding: NHLBI K99HL175100 and R00HL175100 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.