title: Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.
abstract: OBJECTIVE
  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: Center for Cardiovascular Research/Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Berlin, Germany. christa.thoene-reineke@charite.de
authors: Christa
authors: C
authors: Thoene-Reineke
authors: Kay
authors: K
authors: Rumschüssel
authors: Kristin
authors: K
authors: Schmerbach
authors: Maxim
authors: M
authors: Krikov
authors: Christina
authors: C
authors: Wengenmayer
authors: Michael
authors: M
authors: Godes
authors: Susanne
authors: S
authors: Mueller
authors: Arno
authors: A
authors: Villringer
authors: Ulrike
authors: U
authors: Steckelings
authors: Pawel
authors: P
authors: Namsolleck
authors: Thomas
authors: T
authors: Unger
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D008297:Male; D017257:Ramipril / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control*; D000077333:Telmisartan
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D017257:Ramipril; D000077333:Telmisartan