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 used male mice to discern neuronal circuits conferring stress relief and reduced blood pressure. We found that neurons residing in the central nucleus of the amygdala (CeA) expressing angiotensin type 2 receptors (AT₂R), deemed CeA^AT2R, innervate brain nuclei regulating stress responding. 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 AT₂R agonist into the CeA recapitulated the hypotensive and anxiolytic effects, but ablating AT₂R(s) from the CeA was anxiogenic. The results suggest that the excitation of CeA^AT2R couples lowered blood pressure with anxiolysis. The implication is that therapeutics targeting CeA^AT2R may provide stress relief and protection against cardiovascular disease.