Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.

<h4>Objectives</h4>The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.<h4>Methods&l...

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Autores principales:	Christa Thoene-Reineke, Kay Rumschüssel, Kristin Schmerbach, Maxim Krikov, Christina Wengenmayer, Michael Godes, Susanne Mueller, Arno Villringer, Ulrike Steckelings, Pawel Namsolleck, Thomas Unger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38a5750eb981473a868a9e4610d8a1a3
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spelling	oai:doaj.org-article:38a5750eb981473a868a9e4610d8a1a32021-11-18T06:47:16ZPrevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.1932-620310.1371/journal.pone.0023646https://doaj.org/article/38a5750eb981473a868a9e4610d8a1a32011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21901125/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objectives</h4>The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.<h4>Methods</h4>Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0.9% NaCl), (3) T (0.5 mg/kg once daily), (4) R (0.01 mg/kg twice daily), (5) R (0.1 mg/kg twice daily) or (6) T (0.5 mg/kg once daily) plus R (0.01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.<h4>Results</h4>Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.<h4>Conclusions</h4>T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.Christa Thoene-ReinekeKay RumschüsselKristin SchmerbachMaxim KrikovChristina WengenmayerMichael GodesSusanne MuellerArno VillringerUlrike SteckelingsPawel NamsolleckThomas UngerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23646 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christa Thoene-Reineke Kay Rumschüssel Kristin Schmerbach Maxim Krikov Christina Wengenmayer Michael Godes Susanne Mueller Arno Villringer Ulrike Steckelings Pawel Namsolleck Thomas Unger Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
description	<h4>Objectives</h4>The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats.<h4>Methods</h4>Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27), (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0.9% NaCl), (3) T (0.5 mg/kg once daily), (4) R (0.01 mg/kg twice daily), (5) R (0.1 mg/kg twice daily) or (6) T (0.5 mg/kg once daily) plus R (0.01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.<h4>Results</h4>Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.<h4>Conclusions</h4>T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.
format	article
author	Christa Thoene-Reineke Kay Rumschüssel Kristin Schmerbach Maxim Krikov Christina Wengenmayer Michael Godes Susanne Mueller Arno Villringer Ulrike Steckelings Pawel Namsolleck Thomas Unger
author_facet	Christa Thoene-Reineke Kay Rumschüssel Kristin Schmerbach Maxim Krikov Christina Wengenmayer Michael Godes Susanne Mueller Arno Villringer Ulrike Steckelings Pawel Namsolleck Thomas Unger
author_sort	Christa Thoene-Reineke
title	Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
title_short	Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
title_full	Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
title_fullStr	Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
title_full_unstemmed	Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
title_sort	prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/38a5750eb981473a868a9e4610d8a1a3
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Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.

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