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

Comparison of blood pressure-independent neuroprotective effects of systemic pretreatment with candesartan and ramipril following focal cerebral ischemia in rats

Meeting Abstract

  • C. Thöne-Reineke - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin
  • M. Krikov - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin
  • S. Müller - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin
  • C. Neumann - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin
  • A. Villringer - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin
  • T. Unger - Charité Campus Mitte Universitätsmedizin Berlin CCR/Institut für Pharmakologie und Toxikologie, AG Prof. Unger, Berlin

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP53

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch053.shtml

Veröffentlicht: 8. August 2006

© 2006 Thöne-Reineke 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

Potential blood pressure-independent neuroprotective effects of angiotensin AT1 receptor blockade and ACE inhibition in cerebral ischemia were compared using candesartan (C) and ramipril (R) in an experimental model of stroke in normotensive Wistar rats.

Rats were treated with C (2 x 0.1 mg/kg s.c. per day), R (2 x 0.01 mg/kg per day) or vehicle (V; 0.9 % NaCl s.c.) for 5 days before being subjected to 90 min middle cerebral artery occlusion (MCAO) with reperfusion. Doses and regimen were selected on the basis of i) previous evidence of brain protection for C [1], and ii) equal (about 90 %) blockade of pressor responses to i.v. angiotensin II (C) or angiotensin I (R), respectively, for 24 h without affecting systemic blood pressure (BP). BP, cerebral blood flow (CBF) and blood gases were monitored before and during surgery and up to 1 h after reperfusion. After MCAO, neurological deficits were evaluated 24 h and 48 h after reperfusion followed by magnetic resonance imaging (MRI) of infarct volume and subsequent investigation of brain tissue for cellular stress proteins by quantitative real time PCR.

Perisurgical BP, CBF and blood gases were not different between groups. C but not R significantly improved neurological outcome on day 1 and 2 after stroke and reduced infarct volume by about 50 % compared to V. Higher dose of R (2 x 0.1 s.c. per day), which lowered BP during stroke, were also ineffective. C but not R treatment significantly reduced the expression of the stress protein, Hsp70, in the infarct/peri-infarct zone after stroke in comparison to V.

Direct comparison of C and R pretreatment at doses, which equipotently inhibited the renin-angiotensin system in vivo but did not lower BP during stroke, revealed neuroprotection after stroke only with C. The reduced post-ischemic expression of Hsp70 in the C group indicates a limitation of ischemia-induced cellular stress in brain tissue under angiotensin AT1 receptor blockade.


References

1.
Groth et al. J Hypertens. 2003;21:2175-82.