gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Apoptosis is mainly induced in astrocyte but not mediated via angiotensin AT1 receptor after cerebral

Meeting Abstract

  • J. Li - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)
  • C. Thöne-Reineke - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)
  • N. Gerova - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)
  • M. Timm - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)
  • M. Krikov - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)
  • T. Unger - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Belrin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP140

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch140.shtml

Veröffentlicht: 8. August 2006

© 2006 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

Our recent findings suggest that cerebral angiotensin AT2 receptor-mediated neuroprotection is required for the beneficial actions of AT1 receptor antagonist in rat models of brain ischemia. It is unknown whether a direct inhibition of cerebral angiotensin AT1 receptor-mediated actions (i.e. apoptosis) is also contribute to these cerebroprotections of AT1 receptor antagonists. The present study was designed to examine the in vivo role of AT1 receptors in cerebral ischemia-induced apoptosis. We first assessed apoptosis induction in the brain in response to transient unilateral medial cerebral artery occlusion in rats by Western blot analysis and immunofluorescence staining. Forty-eight hours after ischemia, Western blot analysis showed an upregulation of p53 in the peri-infarct zone when compared to sham operated controls. Immunofluorescence staining further revealed that cerebral ischemia induced the expression of cleaved caspase-3 in the peri-infarct zone when compared to c!

ontralateral side or sham operated controls. By double immunofluorescence staining, we could confirm that both AT1 receptor and increased cleaved caspase-3 were mainly located in GFAP+ astrocytes. To clarify the in vivo role of AT1 receptor in astrocyte apoptosis, an AT1 receptor antagonist (candesartan, 0,1 mg/kg) was injected subcutaneously over a period of 5 days before cerebral ischemia. Candesartan significantly improved neurological outcome and reduced the infarct size forty-eight hours after cerebral ischemia. However, the upregulated p53 and cleaved caspase-3 remained unaltered after candesartan treatment. Thus, brain AT1 receptors do not seem to be involved in astrocyte apoptosis following cerebral ischemia. These findings indicate that a direct inhibition of apoptosis in the brain may not play a role in the neuroprotective effects of the AT1 receptor antagonist after cerebral ischemia.