Kim-Mitsuyama Shokei, Yamamoto Eiichiro, Tanaka Tomoko, Zhan Yumei, Izumi Yasukatsu, Izumiya Yasuhiro, Ioroi Takeshi, Wanibuchi Hideki, Iwao Hiroshi
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Stroke. 2005 May;36(5):1083-8. doi: 10.1161/01.STR.0000163084.16505.e3. Epub 2005 Apr 7.
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).
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.
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/mm2; 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.
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.
血管紧张素II在盐加重型卒中中的具体作用尚不清楚。我们研究了血管紧张素II在易患卒中的自发性高血压大鼠（SHRSP）盐加速型卒中中的作用。
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），并比较它们对卒中（n = 61）和脑超氧化物的影响。我们还研究了血管紧张素II输注（每分钟200纳克/千克）对脑超氧化物产生和血脑屏障的影响。
尽管坎地沙坦和氨氯地平的降压效果相当，但坎地沙坦比氨氯地平更能延长盐负荷SHRSP的生存期（P < 0.01），这与坎地沙坦比氨氯地平更能改善SHRSP的脑小动脉增厚、脑小动脉细胞增殖和海马CA1神经元细胞减少（1024.9±20.6对724.9±22.8个细胞/平方毫米；P < 0.01；每组n = 7至10）有关（P < 0.05）。盐负荷增加了SHRSP脑皮质和海马中的超氧化物和NADPH氧化酶活性，而坎地沙坦可阻止这种增加（P < 0.01），但氨氯地平不能。血管紧张素II输注通过AT1受体使盐负荷的SHRSP脑超氧化物直接增加1.8倍（P < 0.05；每组n = 6至7），血脑屏障受损1.7倍（P < 0.05），而tempol和坎地沙坦可阻止脑超氧化物的这种增加和血脑屏障损伤。
过量盐通过氧化应激加速卒中，血管紧张素II通过AT1受体在过量盐导致的SHRSP脑超氧化物产生中起关键作用。
