Abstract | OBJECTIVES: METHODS: 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. RESULTS:
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. CONCLUSIONS: 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.
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Authors | Christa Thoene-Reineke, Kay Rumschüssel, Kristin Schmerbach, Maxim Krikov, Christina Wengenmayer, Michael Godes, Susanne Mueller, Arno Villringer, Ulrike Steckelings, Pawel Namsolleck, Thomas Unger |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 8
Pg. e23646
( 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21901125
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antihypertensive Agents
- Benzimidazoles
- Benzoates
- Ramipril
- Telmisartan
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Topics |
- Animals
- Antihypertensive Agents
(therapeutic use)
- Benzimidazoles
(therapeutic use)
- Benzoates
(therapeutic use)
- Male
- Ramipril
(therapeutic use)
- Random Allocation
- Rats
- Rats, Inbred SHR
- Rats, Wistar
- Stroke
(drug therapy, prevention & control)
- Telmisartan
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