Titre du document / Document title

Hypertension after experimental cerebral ischemia : candesartan provides neurovascular protection

Auteur(s) / Author(s)

FAGAN Susan C. ^{(1 2 3)} ; KOZAK Anna ^{(1 3)} ; HILL William D. ^{(2 3 4)} ; POLLOCK David M. ⁽⁵⁾ ; LIN XU ^{(2 3)} ; JOHNSON Maribeth H. ⁽⁶⁾ ; ERGUL Adviye ^{(1 2 5)} ; HESS David C. ^{(1 2 3)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, ETATS-UNIS
⁽²⁾ Department of Neurology, Veterans Administration Medical Center, Augusta, Georgia, ETATS-UNIS
⁽³⁾ Specialty Care Service Line, Veterans Administration Medical Center, Augusta, Georgia, ETATS-UNIS
⁽⁴⁾ Department of Call Biology and Anatomy, Veterans Administration Medical Center, Augusta, Georgia, ETATS-UNIS
⁽⁵⁾ Vascular Biology Center, Medical College of Georgia, Veterans Administration Medical Center, Augusta, Georgia, ETATS-UNIS
⁽⁶⁾ Department of Biostatistics, Veterans Administration Medical Center, Augusta, Georgia, ETATS-UNIS

Résumé / Abstract

Background After ischemic stroke, hypertension increases the risk of recurrence, hemorrhage and fatal cerebral edema, but blood pressure (BP) lowering in the acute stroke period is controversial due to fears of infarct extension and worsened outcomes. Objective To determine whether BP lowering with candesartan, initiated at reperfusion, can reduce neurovascular damage and improve outcome in a model of hypertension after experimental ischemic stroke. Methods Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either saline (n = 18) or candesartan 1 mg/kg (n = 18) was administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. Neurologic function was assessed and sacrifice occurred at 24 h after occlusion. Brain tissue was analyzed for infarct size, hemoglobin content and edema. Results Mean BP increased from 96 to 124 mmHg immediately upon MCAO and decreased to 114 mmHg after reperfusion, remaining elevated for 24 h (P< 0.001) in the saline group. Candesartan reduced BP back to baseline and BP remained lower than in saline-treated animals until sacrifice (P< 0.001). Infarct size (54 versus 38%, P = 0.01) and hemoglobin content (23.4 versus 10.0 μg/g tissue; P = 0.03) and edema (17.97 versus 11.33%, P< 0.0001) were lower in the candesartan group. In addition, neurologic function at 24 h was improved (P = 0.0036) in the candesartan group. Conclusions Candesartan administered after reperfusion in acute ischemic stroke reduces neurovascular damage and improves outcome.

Revue / Journal Title

Journal of hypertension   ISSN 0263-6352   CODEN JOHYD3 

Source / Source

2006, vol. 24, n^o3, pp. 535-539 [5 page(s) (article)] (24 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott Williams & Wilkins, Hagerstown, MD, ETATS-UNIS  (1983) (Revue)

Mots-clés anglais / English Keywords

Octapeptide ; Peptide hormone ; Vascular disease ; Nervous system diseases ; Central nervous system disease ; Cerebrovascular disease ; Tetrazole derivatives ; AT1 angiotensin receptor ; Biphenyl derivatives ; Benzimidazole derivatives ; Angiotensin antagonist ; Angiotensin II ; Cerebral disorder ; Antihypertensive agent ; Candesartan ; Hypertension ; Stroke ; Ischemia ; Cardiovascular disease ;

Mots-clés français / French Keywords

Sartan dérivé ; Octapeptide ; Hormone peptide ; Vaisseau sanguin pathologie ; Système nerveux pathologie ; Système nerveux central pathologie ; Cérébrovasculaire pathologie ; Tétrazole dérivé ; Récepteur angiotensine AT1 ; Biphényle dérivé ; Benzimidazole dérivé ; Antagoniste angiotensine ; Angiotensine II ; Encéphale pathologie ; Antihypertenseur ; Candésartan ; Hypertension artérielle ; Accident cérébrovasculaire ; Ischémie ; Appareil circulatoire pathologie ;

Mots-clés espagnols / Spanish Keywords

Octapéptido ; Hormona péptido ; Vaso sanguíneo patología ; Sistema nervioso patología ; Sistema nervosio central patología ; Vaso sanguíneo encéfalo patología ; Tetrazol derivado ; Receptor angiotensina AT1 ; Bifenilo derivado ; Benzimidazol derivado ; Antagonista angiotensina ; Angiotensina II ; Encéfalo patología ; Antihipertensivo ; Candesartán ; Hipertensión arterial ; Accidente cerebrovascular ; Isquemia ; Aparato circulatorio patología ;

Mots-clés d'auteur / Author Keywords

candesartan ; hypertension ; stroke ; vascular protection ;

Localisation / Location

INIST-CNRS, Cote INIST : 20680, 35400015682702.0130