Angiotensin protects cortical neurons from hypoxic-induced apoptosis via the angiotensin type 2 receptor

The effects of angiotensin on mouse cortical neuronal cultures exposed to chemical-induced hypoxia was investigated. Cultures exposed to 10 mM sodium azide for 5 min showed a 17% increase in apoptosis when assayed 24 h postinsult. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked sodium azide-induced cell death suggesting that the NMDA receptor contributes to the mediated cell death. Pretreatment of cultured neurons with angiotensin decreased sodium azide-induced apoptosis by 94%. When the AT₁ receptor was blocked by its receptor antagonist, losartan, angiotensin activation of the AT₂ receptor completely inhibited sodium azide-induced apoptosis. Pretreatment of neurons with the AT₂ receptor antagonist PD123319 resulted in angiotensin reducing sodium azide-induced apoptosis by 48%. These results demonstrate that angiotensin can significantly attenuate sodium azide-induced apoptosis primarily through activation of the AT₂ receptor and suggests that angiotensin may have a protective role in neurons undergoing ischemic injury.