Angiotensin II and angiotensin-(1-7) neurotransmissions in the medial amygdala differently control cardiovascular and anxiogenic-like responses to stress in rats.

BackgroundThe medial amygdala nucleus (MeA) has been implicated in stress responses. However, the local neurochemical mechanisms involved are not completely understood.AimsThis study examined how angiotensin II and angiotensin-(1-7) neurotransmissions within the MeA contribute to cardiovascular, autonomic, and anxiogenic-like responses to acute restraint stress (ARS) and repeated restraint stress (RRS) in rats.MethodsSelective angiotensinergic receptor antagonists and agonists were microinjected into the MeA, and physiological and behavioral responses were evaluated during ARS and the 10th restraint session (i.e., RRS).ResultsDuring ARS, tachycardia was potentiated by angiotensin II, the AT1 receptor antagonist losartan, and angiotensin-(1-7), whereas antagonism of AT2 receptors with PD123319 or Mas receptors with A-779 attenuated this effect. AT2 receptor antagonism also reduced the pressor response and sympathetically mediated cutaneous vasoconstriction. In addition, angiotensin II, losartan, and angiotensin-(1-7) reduced the anxiogenic-like behavior in the elevated plus maze following ARS. RRS did not affect gene expression of angiotensinergic receptors in the MeA. Consistently, angiotensin-(1-7) produced similar effects during ARS and the 10th restraint session. However, contrary to findings obtained in acutely stressed animals, angiotensin II and losartan failed to influence responses during the 10th restraint session. Interestingly, AT2 receptor antagonism, which reduced tachycardia in ARS, enhanced it under chronic stress.ConclusionsThese findings indicate that angiotensin II/AT1-AT2 receptors and angiotensin-(1-7)/Mas receptor axes within the MeA regulate cardiovascular and anxiety-related responses to acute stress, and their roles are influenced by repeated stress exposure.