Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection
Blood pressure lowering after experimental cerebral ischemia provides neurovascular protection
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DOI：
10.1097/hjh.0b013e3280149708
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Fagan, Susan C.
中科院分区：
文献类型：
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作者：
Elewa, Hazem F.;Kozak, Anna;Fagan, Susan C.
研究背景有证据表明卒中后急性血压升高与脑出血和水肿增加有关。我们实验室之前的实验表明，坎地沙坦在实验性缺血性卒中后的高血压模型中再灌注后给予1mg /kg可减少神经血管损伤并改善预后。这些结果可能是由血压降低或不依赖于血压的脑血管保护作用介导的。目的探讨坎地沙坦降低血压对脑卒中后神经血管的保护作用。方法雄性Wistar大鼠（280 ~ 305 g）脑中动脉闭塞3 h。再灌注时，静脉滴注肼1 mg/kg （n=8）、依那普利5 mg/kg （n=7）或依那普利10 mg/kg （n=8）。在MCAO前2 d和术后24 h遥测血压。评估神经功能后，对脑组织进行梗死面积和血红蛋白含量分析。结果生理盐水组的平均动脉压（MAP）在MCAO后立即由92升高至124 mmHg，再灌注后降至112 mmHg，并持续24 h升高（P < 0.0001）。海氮嗪可降低MAP （P=0.048）和梗死面积（53%比30%，P=0.0083），并有降低血红蛋白含量的趋势。依那普利5mg /kg没有显著改变MAP或其他结果。依那普利10 mg/kg可降低MAP （P < 0.0001）和梗死面积（53%对29%，P=0.003）。对血红蛋白含量和神经功能均有中间影响，但均不显著。降压的时间随治疗的不同而不同。结论急性缺血性脑卒中再灌注后急性降血压是实现神经血管保护的有效策略。血压降低的速度、程度和机制可能决定保护的程度。
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.