title: Angiotensin protects cortical neurons from hypoxic-induced apoptosis via the angiotensin type 2 receptor.
abstract: 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 AT(1) receptor was blocked by its receptor antagonist, losartan, angiotensin activation of the AT(2) receptor completely inhibited sodium azide-induced apoptosis. Pretreatment of neurons with the AT(2) 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 AT(2) receptor and suggests that angiotensin may have a protective role in neurons undergoing ischemic injury.
authors.affiliation: Department of Cell and Structural Biology, University of Illinois, B107 Chemical and Life Science Building, 601 S. Goodwin Ave, Urbana, IL 61801, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Grammatopoulos
authors.forename: Katherine
authors.initials: K
authors.lastname: Morris
authors.forename: Paul
authors.initials: P
authors.lastname: Ferguson
authors.forename: James
authors.initials: J
authors.lastname: Weyhenmeyer
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D019810:Sodium Azide / Q000494:pharmacology; D014343:Trypan Blue; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D016194:Receptors, N-Methyl-D-Aspartate; D014665:Vasodilator Agents; C073402:PD 123319; D019810:Sodium Azide; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue; D019808:Losartan