Abstract | BACKGROUND AND PURPOSE: We have shown that acute treatment with candesartan in an experimental model of stroke resulted in vascular protection and improved outcomes at 24 hours poststroke, but the mechanisms are unknown. We now examine effects of candesartan on proangiogenic factors and 7-day outcomes using the same treatment paradigm. METHODS: RESULTS:
Matrix metalloproteinase-2 activity and vascular endothelial growth factor expression were higher (P=0.035, P=0.042, respectively) and cerebrospinal fluid was significantly more proangiogenic (5x tube formation; P=0.002) in the candesartan group at 24 hours. Although no difference was seen in infarct size at 7 days, treatment improved Bederson scores (2.1 versus 2.9, P=0.0083), elevated body swing test (22.9 versus 39.4, P=0.021), and paw grasp (1.29 versus 2.88, P=0.0001) at 7 days. Candesartan treatment resulted in increased vascular density in the striatum at 7 days (P=0.037). CONCLUSIONS:
Candesartan after reperfusion augments ischemia-induced angiogenic state and provides long-term benefits. The beneficial effects may involve vascular protection and enhancement of early angiogenic remodeling.
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Authors | Anna Kozak, Adviye Ergul, Azza B El-Remessy, Maribeth H Johnson, Livia S Machado, Hazem F Elewa, Mohammed Abdelsaid, Daniel C Wiley, Susan C Fagan |
Journal | Stroke
(Stroke)
Vol. 40
Issue 5
Pg. 1870-6
(May 2009)
ISSN: 1524-4628 [Electronic] United States |
PMID | 19265050
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Benzimidazoles
- Biphenyl Compounds
- Laminin
- Tetrazoles
- Vascular Endothelial Growth Factor A
- Matrix Metalloproteinases
- candesartan
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(pharmacology)
- Animals
- Behavior, Animal
(physiology)
- Benzimidazoles
(pharmacology)
- Biphenyl Compounds
- Blood Pressure
(physiology)
- Body Weight
(physiology)
- Brain Ischemia
(complications, drug therapy, psychology)
- Capillary Permeability
(drug effects)
- Endothelial Cells
(pathology)
- Infarction, Middle Cerebral Artery
(pathology)
- Laminin
(metabolism)
- Male
- Matrix Metalloproteinases
(biosynthesis)
- Microtubules
(pathology)
- Neovascularization, Physiologic
(drug effects)
- Rats
- Rats, Wistar
- Stroke
(drug therapy, etiology, psychology)
- Tetrazoles
(pharmacology)
- Vascular Endothelial Growth Factor A
(biosynthesis, metabolism)
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