Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Elewa
Hazem F
HF
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta 30912-2450, USA.
Kozak
Anna
A
Johnson
Maribeth H
MH
Ergul
Adviye
A
Fagan
Susan C
SC
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology; D006454:Hemoglobins / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013686:Telemetry; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D006454:Hemoglobins; D013777:Tetrazoles; D006830:Hydralazine; D004656:Enalapril; C081643:candesartan