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

Abstract

OBJECTIVES:

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.

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.

• 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)

Chemical References

• Antihypertensive Agents
• Benzimidazoles
• Benzoates
• Ramipril
• Telmisartan

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