Postischemic administration of angiotensin II type 1 receptor blocker reduces cerebral infarction size in hypertensive rats
Postischemic administration of angiotensin II type 1 receptor blocker reduces cerebral infarction size in hypertensive rats
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DOI：
10.1038/hr.2009.69
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发表时间：
2009-07-01
影响因子：
5.4
通讯作者：
Kitagawa, Kazuo
中科院分区：
文献类型：
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作者：
Omura-Matsuoka, Emi;Yagita, Yoshiki;Kitagawa, Kazuo
在缺血性卒中后急性期降低血压（BP）仍然是一个有争议的治疗方法。在这项研究中，我们研究了缺血后使用血管紧张素II 1型受体阻滞剂坎地沙坦治疗对局灶性脑缺血脑损伤的影响。自发性高血压大鼠短暂性大脑中动脉闭塞1 h。坎地沙坦（0.1，1和10 mg/kg）或溶剂在缺血后3和24 h口服给药。监测血压和神经功能，并在闭塞后48小时评估梗死体积。用激光多普勒血流仪测定坎地沙坦治疗前后脑血流。采用免疫组化法检测脑微血管Rho激酶活性。中剂量和高剂量的坎地沙坦均能显著降低收缩压，但低剂量的坎地沙坦不能降低收缩压。低剂量坎地沙坦治疗组大鼠的梗死体积减少，但中剂量或高剂量治疗组大鼠的梗死体积没有减少。与溶媒相比，使用中等剂量坎地沙坦治疗后3 h，脑血流量降低与BP降低平行，但使用低剂量坎地沙坦治疗后，脑血流量未发生变化。Rho激酶在缺血皮质的脑血管中被激活，但坎地沙坦治疗抑制了它。我们的研究结果表明，短暂性局灶性缺血后口服坎地沙坦可减少梗死体积，剂量对BP影响不大。坎地沙坦的神经血管保护作用可能与抑制脑微血管Rho激酶有关。高血压研究（2009）32，548-553; doi：10.1038/hr.2009.69; 2009年5月8日在线发表
Lowering the blood pressure ( BP) during the acute period following ischemic stroke is still a controversial treatment. In this study, we investigated the effect of postischemic treatment using the angiotensin II type 1 receptor blocker, candesartan, on brain damage in focal cerebral ischemia. Spontaneously hypertensive rats underwent transient occlusion of the middle cerebral artery for 1 h. Candesartan ( 0.1, 1 and 10 mg kg(-1)) or vehicle was administered orally 3 and 24 h after ischemia. Blood pressure and neurological function were monitored, and infarct volume was evaluated 48 h after occlusion. Cerebral blood flow was measured using laser Doppler flowmetry before and after treatment with candesartan. Activation of Rho-kinase in cerebral microvessels was evaluated by immunohistochemistry. Systolic blood pressure was markedly lowered with both moderate and high doses, but it did not fall with a low dose of candesartan. The infarct volume was reduced in rats treated with the low dose of candesartan but not in those treated with the moderate or high doses. Cerebral blood flow decreased in parallel with the reduction in BP 3 h after treatment using the moderate dose, but it did not change after treatment with the low dose of candesartan, compared with vehicle. Rho-kinase was activated in the brain vessels of the ischemic cortex, but treatment with candesartan suppressed it. Our results show that oral administration of candesartan after transient focal ischemia reduced infarct volume at doses that showed little effect on BP. The neurovascular protective effects of candesartan may be caused by the inhibition of Rho-kinase in brain microvessels. Hypertension Research ( 2009) 32, 548-553; doi: 10.1038/hr.2009.69; published online 8 May 2009