Hypertension after experimental cerebral ischemia: candesartan provides neurovascular protection.
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 microg/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.
Fagan
Susan C
SC
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia 30912-2450, USA. sfagan@mail.mcg.edu
Kozak
Anna
A
Hill
William D
WD
Pollock
David M
DM
Xu
Lin
L
Johnson
Maribeth H
MH
Ergul
Adviye
A
Hess
David C
DC
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000517:prevention & control*; D001929:Brain Edema / Q000517:prevention & control; D020520:Brain Infarction / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D006454:Hemoglobins / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006454:Hemoglobins; D013777:Tetrazoles; C081643:candesartan