Document Detail

Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection.
MedLine Citation:
PMID:  17351379     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: There is evidence that acutely elevated blood pressure (BP) after stroke is associated with increased cerebral hemorrhage and edema. Previous experiments in our laboratory have shown that candesartan 1 mg/kg administered after reperfusion in a model of hypertension after experimental ischemic stroke reduces neurovascular damage and improves outcome. These results could be either mediated by BP lowering or a BP-independent cerebrovascular protective effect.
OBJECTIVES: To determine the contribution of BP lowering to the neurovascular protection previously reported with candesartan after stroke.
METHODS: Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either hydralazine 1 mg/kg (n = 8), enalapril 5 mg/kg (n = 7) or enalapril 10 mg/kg (n = 8) were administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. After neurological function was assessed, brain tissue was processed for infarct size and hemoglobin content analyses.
RESULTS: Mean arterial pressure (MAP) increased from 92 to 124 mmHg immediately upon MCAO and decreased to 112 mmHg after reperfusion, remaining elevated for 24 h (P < 0.0001) in the saline group. Hydralazine reduced MAP (P = 0.048) and infarct size (53 versus 30%, P = 0.0083), and there was a trend towards decreased hemoglobin content. Enalapril 5 mg/kg did not significantly change MAP or other outcomes. Enalapril 10 mg/kg reduced MAP (P < 0.0001) and infarct size (53 versus 29%, P = 0.003). There was an intermediate effect on both hemoglobin content and neurological function, neither one was significant. The time course of BP lowering varied with each treatment.
CONCLUSION: Acute BP lowering after reperfusion in acute ischemic stroke is an effective strategy to achieve neurovascular protection. The rate, extent and mechanism of BP lowering may determine the magnitude of protection.
Hazem F Elewa; Anna Kozak; Maribeth H Johnson; Adviye Ergul; Susan C Fagan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  25     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-12     Completed Date:  2007-08-07     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  855-9     Citation Subset:  IM    
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta 30912-2450, USA.
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MeSH Terms
Analysis of Variance
Angiotensin II Type 1 Receptor Blockers / pharmacology
Antihypertensive Agents / pharmacology*
Area Under Curve
Benzimidazoles / pharmacology
Biological Markers / blood
Blood Pressure / drug effects*
Brain Ischemia / etiology,  physiopathology*,  prevention & control*
Cerebrovascular Circulation / drug effects
Circadian Rhythm / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Enalapril / administration & dosage,  pharmacology
Hemoglobins / drug effects
Hydralazine / pharmacology
Infarction, Middle Cerebral Artery / complications,  physiopathology
Rats, Wistar
Tetrazoles / pharmacology
Grant Support
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Biological Markers; 0/Hemoglobins; 0/Tetrazoles; 75847-73-3/Enalapril; 86-54-4/Hydralazine; S8Q36MD2XX/candesartan
Comment In:
J Hypertens. 2007 Apr;25(4):743-5   [PMID:  17351363 ]

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