Neurons of the central nucleus of the amygdala that express angiotensin type 2 receptors couple lowered blood pressure with anxiolysis in male mice

Relief from psychological stress confers cardio-protection by altering brain activity and lowering blood pressure; however, the neuronal circuits orchestrating these effects are unknown. Here, we test the hypothesis that neurons within the central nucleus of the amygdala that express angiotensin type 2 receptors (hereafter referred to as CeA AT2R ) engage neuronal circuits that confer stress relief and reduced blood pressure. Using mice genetically-engineered to have enhanced green fluorescent protein (eGFP) or Cre-recombinase directed to cells that express AT2R, we revealed that CeA AT2R are primarily GABAergic, excited by an AT2R agonist (C21), and connected to fore-, mid-, and hindbrain nuclei mediating autonomic outflow and stress reactivity. In vivo optogenetic excitation of CeA AT2R lowered blood pressure and this effect was abrogated by systemic hexamethonium or antagonism of GABA receptors within the CeA. Intriguingly, in vivo optogenetic excitation of CeA AT2R was also potently anxiolytic. Delivery of an AT 2 R agonist into the CeA recapitulated the hypotensive and anxiolytic effects, but ablating AT 2 R(s) from the CeA was anxiogenic. The results suggest that the excitation of CeA AT2R couples lowered blood pressure with anxiolysis. The conclusion is that therapeutics targeting CeA AT2R may provide stress relief and protection against cardiovascular disease. NIH: R35HL150750 (EGK), R01HL145028 (AdK), and K99HL175100 (KE). AHA: 23POST1020034 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.