Critical role of angiotensin II in excess salt-induced brain oxidative stress of stroke-prone spontaneously hypertensive rats
Critical role of angiotensin II in excess salt-induced brain oxidative stress of stroke-prone spontaneously hypertensive rats
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DOI：
10.1161/01.str.0000163084.16505.e3
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发表时间：
2005-05-01
期刊：
影响因子：
8.3
通讯作者：
Iwao, H
中科院分区：
文献类型：
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作者：
Kim-Mitsuyama, S;Yamamoto, E;Iwao, H
背景和目的 - 血管紧张素 II 在盐加剧中风中的详细作用尚不清楚。我们检查了血管紧张素II在易发生卒中的自发性高血压大鼠（SHRSP）的盐加速卒中中的作用。方法-给盐负荷的SHRSP口服血管紧张素II 1型（AT1）受体阻滞剂坎地沙坦（每天0.3至3毫克/千克）和钙通道阻滞剂氨氯地平（每天1毫克/千克），并观察对卒中（n = 61）和脑超氧化物的影响。他们之间进行比较。我们还检测了血管紧张素 II 输注（200 ng/kg/min）对脑超氧化物产生和血脑屏障的影响。 结果 - 尽管坎地沙坦和氨氯地平的降血压作用相当，但坎地沙坦比氨氯地平更能延长盐负载 SHRSP 的生存时间（P < 0.01），并且与脑小动脉增厚、脑小动脉细胞增殖和海马 CA1 的改善有关。与氨氯地平相比，坎地沙坦 SHRSP 中神经元细胞减少（1024.9 +/- 20.6 与 724.9 +/- 22.8 细胞/mm(2)；P < 0.01；每组 n = 7 至 10）（P < 0.05）。盐负荷增加了SHRSP大脑皮层和海马中的超氧化物和NADPH氧化酶活性，坎地沙坦可以阻止这种增加（P < 0.01），但氨氯地平不能阻止这种增加。血管紧张素 II 输注通过 AT1 受体，直接使脑超氧化物增加 1.8 倍（P < 0.05；每组 n = 6 至 7），并使含盐 SHRSP 中的血脑屏障受损达 1.7 倍（P < 0.05），而 tempol 和坎地沙坦可以防止脑超氧化物的增加和血脑屏障受损。结论 - 过量的盐通过氧化应激，加速中风，血管紧张素 II 通过 AT1 受体，在过量盐引起的 SHRSP 脑超氧化物生成中发挥关键作用。
Background and Purpose - The detailed role of angiotensin II in salt-exacerbated stroke is unclear. We examined the role of angiotensin II in salt-accelerated stroke of stroke-prone spontaneously hypertensive rats (SHRSP).Methods - Salt- loaded SHRSP were orally given the angiotensin II type 1 (AT1) receptor blocker candesartan ( 0.3 to 3 mg/kg per day) and calcium channel blocker amlodipine ( 1 mg/kg per day), and the effects on stroke ( n = 61) and brain superoxide were compared between them. We also examined the effect of angiotensin II infusion ( 200 ng/kg per min) on brain superoxide production and blood - brain barrier.Results - Despite the comparable hypotensive effect between candesartan and amlodipine, candesartan prolonged survival of salt-loaded SHRSP much more than amlodipine ( P < 0.01), being associated with more improvement of cerebral arteriolar thickening, cerebral arteriolar cell proliferation, and hippocampal CA1 neuronal cell reduction (1024.9 +/- 20.6 versus 724.9 +/- 22.8 cells/mm(2); P < 0.01; n = 7 to 10 in each group) in SHRSP by candesartan ( P < 0.05) than amlodipine. Salt loading increased superoxide and NADPH oxidase activity in brain cortex and hippocampus of SHRSP, and this increase was prevented by candesartan ( P < 0.01) but not amlodipine. Angiotensin II infusion, via AT1 receptor, directly increased brain superoxide by 1.8-fold ( P < 0.05; n = 6 to 7 in each group) and impaired blood - brain barrier in salt-loaded SHRSP by 1.7-fold ( P < 0.05), and this increase in brain superoxide and blood - brain barrier impairment was prevented by tempol as well as candesartan.Conclusion - Excess salt, via oxidative stress, accelerates stroke, and angiotensin II, via AT1 receptor, plays a pivotal role in brain superoxide production of SHRSP by excess salt.