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 (AT 2 R), 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 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 implication is that therapeutics targeting CeA AT2R may provide stress relief and protection against cardiovascular disease. Significance statement There is increasing appreciation that brain-to-body communication promotes susceptibility or resiliency to cardiovascular disease. Here, we present preclinical research that discerns a neural circuit that orchestrates brain-to-body communication and provides relief from mental stress. We discover that neurons within the central nucleus of the amygdala that express angiotensin type 2 receptors (hereafter referred to as CeA AT2R ) are potent mediators of blood pressure and anxiolysis. The implication is that CeA AT2R or their angiotensin type 2 receptors can be targeted to protect against stress-induced cardiovascular disease.