Arterial baroreceptors innervating the aortic arch utilize ENaC and TRPA1 channels in baroreception

The brain maintains blood pressure, in part, via arterial baroreceptors that innervate the aortic arch. Arterial baroreceptors convert stretch exerted on the arterial wall into action potentials carried by the vagus nerve to second order neurons residing within the nucleus of the solitary tract (NTS). Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of arterial baroreceptors remain uncharacterized. This is due to the lack of tools that provide the genetic and target organ specificity that is required to selectively characterize arterial baroreceptors. Here, we use a novel approach to selectively target arterial baroreceptors that innervate the aortic arch. Male 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 channelrhoropsin-2 (ChR2) and/or tdTomato (tdTom) to arterial baroreceptors. Consistent with the structural characteristics of arterial 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 of the nodose ganglia (NDG), and neural projections to the caudal NTS (cNTS). Additionally, the tdTom labeled cell bodies within the NDG also expressed mRNAs coding for the mechanically gated ion channels, PIEZO-1 and PIEZO-2. In vivo optogenetic stimulation of the cell bodies of arterial baroreceptors produced robust depressor responses. These results validate that our approach selectively targets arterial baroreceptors innervating the aortic arch. Utilizing this approach, we found subsets of tdTom labeled cell bodies within the NDG that expressed mRNAs coding for epithelial sodium channels (ENaC) and transient potential ankyrin 1 (TRPA1) channels. To ascertain the functionality of these channels, we locally applied 2M sodium chloride or 4-ethyl-2-methyl-2-thiazoline (4E2MT; TRPA1 agonist) to the aortic arch and observed depressor responses in anaesthetized mice. Taken together, we utilized a novel approach to selectively label arterial baroreceptors and found that activation of ENaC and TRPA1channels is sufficient to evoke baroreception. AHA 23POST1020034 and NHLBI K99HL175100 to KE. NHLBI R01HL136595, R35HL150750, R01HL145028 and NCCIH R65AT012142 to ADK & EGK. This abstract was presented at the American Physiology Summit 2025 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.