gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury

Meeting Abstract (Hypertonie 2004)

  • J. Li - Center for Cardiovascular Research (CCR) Berlin, D
  • J. Culman - Institute of Pharmacology, UKSH, Campus Kiel (Kiel, D)
  • H. Hörtnagl - Center for Cardiovascular Research (CCR) Berlin, D
  • Y. Zhao - Institute of Pharmacology, UKSH, Campus Kiel (Kiel, D)
  • N. Gerova - Center for Cardiovascular Research (CCR) Berlin, D
  • M. Timm - Center for Cardiovascular Research (CCR) Berlin, D
  • A. Blume - Center for Cardiovascular Research (CCR) Berlin, D
  • M. Zimmermann - Center for Cardiovascular Research (CCR) Berlin, D
  • K. Seidel - Center for Cardiovascular Research (CCR) Berlin, D
  • U. Dirnagl - University Hospital, Department of Experimental Neurology (Berlin, D)
  • T. Unger - Center for Cardiovascular Research (CCR) Berlin, D

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP14

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch014.shtml

Veröffentlicht: 10. August 2005

© 2005 Li et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Several lines of clinical and experimental evidence suggest an important role of the renin-angiotensin system in ischemic brain injury although the cellular regulation of the angiotensin AT1 and AT2 receptors and their potential relevance in this condition have not yet been clearly defined. We first assessed the regulation of brain AT1 and AT2 receptors in response to transient unilateral medial cerebral artery occlusion in rats by real-time RT-PCR, Western blot and immunofluorescence labelling. AT2 receptors in the peri-infarct zone were significantly upregulated 2 days following transient focal cerebral ischemia. Increased AT2 receptors, which were abundantly distributed in a large number of brain regions adjacent to the infarct area including cerebral frontal cortex, piriform cortex, striatum and hippocampus, were exclusively expressed in neurons. By contrast, AT1 receptors, which remained unaltered, were mainly expressed in astrocytes. In neurons of ischemic striatum, increased AT2 receptors were associated with intense neurite outgrowth. Blockade of central AT2 receptors with PD 123177 abolished the neuroprotective effects of central AT1 receptor blockade with irbesartan on infarct size and neurological outcome. In primary cortical neurons, stimulation of AT2 receptors supported neuronal survival and neurite outgrowth. Our data indicate that cerebral AT2 receptors exert neuroprotective actions in response to ischemia-induced neuronal injury, possibly by supporting neuronal survival and neurite outgrowth in peri-ischemic brain areas.