Oxytocin receptor expressing neurons utilize Piezo2 to mediate the baroreflex in female mice
Authors: Johnson Dominique , Elsaafien Khalid , Scott Karen , de Kloet Annette , Krause Eric 
Published: May 2024

Oxytocin is a neuropeptide in clinical trials for mental health disorders that is also reported to have beneficial effects on cardiovascular function. Arterial baroreceptors contribute to cardiovascular function by relaying information pertaining to perfusion pressure to the brain. Neurons that give rise to arterial baroreceptors reside in the nodose ganglion (NG). These neurons utilize Piezo2, a mechanosensitive ion channel, to convert pressure and stretch exerted on the vascular wall of the aortic arch into action potentials that are carried by the vagus nerve to the brain. Upon receiving this information, the brain initiates the baroreflex which adjusts cardiac output and vasculature resistance to maintain blood pressure at optimal levels. Interestingly, we have determined that a subpopulation of NG neurons express both the oxytocin receptor (Oxtr) and Piezo2. Here, we test the overall hypothesis that Piezo2 synthesized by Oxtr-expressing neurons mediate cardiovascular function in male and female mice. Mice that express Cre-recombinase at the Oxtr locus were bred to mice with LoxP sites flanking the Piezo2 gene. This resulted in offspring with the Piezo2 gene selectively deleted from cells that express the Oxtr gene (Oxtr Piezo2 KO) or littermates only harboring LoxP sites flanking the Piezo2 gene (controls). To validate the selective deletion of Piezo2 from neurons that express Oxtr, we used RNAscope in situ hybridization to label Oxtr and Piezo2 mRNAs within the NG. In control mice, we frequently observed NG neurons double-labeled for Oxtr and Piezo2 mRNAs. In contrast, colocalization of these mRNAs was not observed in NG neurons obtained from OxtrPiezo2 KO mice. Cardiovascular recordings were performed in anesthetized mice administered the vasoactive drug phenylephrine (PE; i.v.) to determine whether deletion of Piezo2 from Oxtr-expressing neurons affects blood pressure, heart rate, and the baroreflex. Baseline systolic blood pressure was lower in male OxtrPiezo2 KO mice compared to controls but resting heart rate was similar amongst the groups. Pressor and bradycardic responses to PE were not different between male OxtrPiezo2 KO mice and controls, suggesting that deletion of Piezo2 from Oxtr-expressing neurons has no effect on the baroreflex in male mice. Female OxtrPiezo2 KO mice had baseline systolic blood pressure and heart rate that were similar to controls. In females, delivery of PE similarly increased systolic blood pressure in OxtrPiezo2 KO mice and controls, but remarkably, the significant bradycardia that was observed in control mice was completely absent in female OxtrPiezo2 KO mice. Collectively, these results suggest that Piezo2 expression in neurons that synthesize Oxtr is necessary to evoke the baroreflex specifically in female mice. AHA 23POST1020034 to KE. NHLBI R01HL136595, R35HL150750, R01HL145028 and NCCIH R65AT012142 to ADK & EGK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.