Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.

<h4>Objective</h4>Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects.<h4>Methods</h4>Since aliskiren spec...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristin Schmerbach, Thiemo Pfab, Yi Zhao, Juraj Culman, Susanne Mueller, Arno Villringer, Dominik N Muller, Berthold Hocher, Thomas Unger, Christa Thoene-Reineke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a64bb0513bc24d7cb3d3592a97a31ed7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a64bb0513bc24d7cb3d3592a97a31ed7
record_format	dspace
spelling	oai:doaj.org-article:a64bb0513bc24d7cb3d3592a97a31ed72021-11-18T07:36:28ZEffects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.1932-620310.1371/journal.pone.0015052https://doaj.org/article/a64bb0513bc24d7cb3d3592a97a31ed72010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124781/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects.<h4>Methods</h4>Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kgd) or candesartan (1.5 or 10 mg/kgd) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions.<h4>Results</h4>The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core.<h4>Conclusions</h4>Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further.Kristin SchmerbachThiemo PfabYi ZhaoJuraj CulmanSusanne MuellerArno VillringerDominik N MullerBerthold HocherThomas UngerChrista Thoene-ReinekePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e15052 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristin Schmerbach Thiemo Pfab Yi Zhao Juraj Culman Susanne Mueller Arno Villringer Dominik N Muller Berthold Hocher Thomas Unger Christa Thoene-Reineke Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
description	<h4>Objective</h4>Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects.<h4>Methods</h4>Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kgd) or candesartan (1.5 or 10 mg/kgd) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions.<h4>Results</h4>The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core.<h4>Conclusions</h4>Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further.
format	article
author	Kristin Schmerbach Thiemo Pfab Yi Zhao Juraj Culman Susanne Mueller Arno Villringer Dominik N Muller Berthold Hocher Thomas Unger Christa Thoene-Reineke
author_facet	Kristin Schmerbach Thiemo Pfab Yi Zhao Juraj Culman Susanne Mueller Arno Villringer Dominik N Muller Berthold Hocher Thomas Unger Christa Thoene-Reineke
author_sort	Kristin Schmerbach
title	Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
title_short	Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
title_full	Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
title_fullStr	Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
title_full_unstemmed	Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
title_sort	effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/a64bb0513bc24d7cb3d3592a97a31ed7
work_keys_str_mv	AT kristinschmerbach effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT thiemopfab effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT yizhao effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT jurajculman effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT susannemueller effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT arnovillringer effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT dominiknmuller effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT bertholdhocher effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT thomasunger effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes AT christathoenereineke effectsofaliskirenonstrokeinratsexpressinghumanreninandangiotensinogengenes
_version_	1718423240334901248

Effects of aliskiren on stroke in rats expressing human renin and angiotensinogen genes.

Ejemplares similares