Vascular protection with candesartan after experimental acute stroke in hypertensive rats: A dose-response study
Vascular protection with candesartan after experimental acute stroke in hypertensive rats: A dose-response study
复制标题
DOI：
10.1124/jpet.108.139618
复制
发表时间：
2008-09-01
影响因子：
3.5
通讯作者：
Fagan, Susan C.
中科院分区：
文献类型：
--
作者：
Kozak, Wieslaw;Kozak, Anna;Fagan, Susan C.
我们已经证明坎地沙坦可降低Wistar大鼠急性卒中引起的平均动脉压(MAP)升高，并改善功能结局。本研究的目的是确定在自发性高血压大鼠(SHR)中是否也能获得同样的好处。大鼠大脑中动脉闭塞(MCAO)或假手术3h后再灌注。给予坎地沙坦(0.1、0.3或1.0 mg/kg)或生理盐水。用遥测的方法监测大鼠的MAP，并进行神经功能评定。在卒中后24小时评估缺血区的梗塞范围、水肿形成和血红蛋白含量。SHR MAP在MCAO后即刻由135(基线)升至189 mm Hg，并持续升高至再灌流。坎地沙坦以剂量依赖的方式降低MAP，1.0 mg/kg剂量后降至基线以下。与假手术组相比，卒中后应用坎地沙坦的自发性高血压大鼠的降压效果更好(p<；0.0001)。坎地沙坦治疗的动物中风后神经功能缺陷减少，表现出剂量依赖效应(p<；0.01)。坎地沙坦0.1 mg/kg和0.3 mg/kg剂量均能减少脑梗塞面积、水肿形成和血红蛋白含量(p<；0.05)。坎地沙坦(1 mg/kg)与生理盐水无明显差异。小剂量坎地沙坦对自发性高血压大鼠卒中后的神经血管有保护作用。谨慎是有必要的，因为急性中风增加了对血压下降的敏感性，这反过来又增加了过度射击的可能性。
We have shown that candesartan decreases the acute stroke-induced elevation of mean arterial blood pressure (MAP) in Wistar rats and improves functional outcome. The aim of the present study was to determine whether the same benefit could be achieved in spontaneously hypertensive rats (SHR). Animals were subjected to middle cerebral artery occlusion (MCAO) or sham for 3 h followed by reperfusion. Either candesartan (0.1, 0.3, or 1.0 mg/kg) or saline was administered. MAP of the rats was monitored by means of telemetry, and neurological function was assessed. Infarct size, edema formation, and hemoglobin content in the ischemic hemisphere were evaluated 24 h after the stroke. MAP of SHR increased immediately upon MCAO from 135 (baseline) to 189 mm Hg, and it remained elevated until reperfusion. Candesartan decreased MAP in a dose-dependent manner, with a drop below baseline after a dose of 1.0 mg/kg. SHRs experienced greater blood pressure (BP)-lowering effects of candesartan after stroke compared with a sham condition (p < 0.0001). Neurological deficit after stroke was reduced in candesartan-treated animals, revealing a dose-dependent effect (p < 0.01). Infarct size, edema formation, and hemoglobin content were all reduced by candesartan at doses of 0.1 and 0.3 mg/kg (p < 0.05 for all). Candesartan (1 mg/kg) was not different from saline. Low doses of candesartan provide neurovascular protection after stroke in SHRs. Caution is warranted because acute stroke increases the sensitivity to BP lowering, which, in turn, increases the likelihood of over-shooting.