Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation
Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation
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DOI：
10.1161/01.cir.0000138848.58269.80
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发表时间：
2004-08-17
期刊：
影响因子：
37.8
通讯作者：
Horiuchi, M
中科院分区：
文献类型：
--
作者：
Iwai, M;Liu, HW;Horiuchi, M
背景：研究了血管紧张素II受体亚型在大脑中动脉闭塞引起的局灶性脑缺血中的作用。方法与结果- Agtr2(+)（野生型）小鼠，MCA闭塞引起脑冠状区约20% ~ 30%的局部缺血。血管紧张素II 2型受体缺陷（Agtr2(-)）小鼠的缺血区域明显大于Agtr2（+）小鼠。Agtr2（-）小鼠MCA闭塞后的神经功能缺损也比Agtr2（+）小鼠更大。Agtr2（-）小鼠MCA闭塞后脑表面血流量的减少在MCA区域的外周区域被显著夸大。Agtr2（-）小鼠脑缺血区超氧化物生成和NADPH氧化酶活性增强。AT(1)受体阻滞剂缬沙坦在非降压剂量下显著抑制Agtr2（+）小鼠的缺血区域、神经功能缺损、脑血流量减少、超氧化物产生和NADPH氧化酶活性。缬沙坦对Agtr2（-）小鼠的抑制作用较弱。结论：这些结果表明，AT(2)受体刺激对缺血性脑损伤具有保护作用，至少部分是通过调节脑血流和超氧化物的产生。
Background-The role of angiotensin II receptor subtypes was investigated in focal brain ischemia induced by middle cerebral artery (MCA) occlusion.Methods and Results-In Agtr2(+) (wild-type) mice, MCA occlusion induced focal ischemia of approximate to20% to 30% of the total area in coronal section of the brain. The ischemic area was significantly larger in angiotensin II type 2 receptor-deficient (Agtr2(-)) mice than in Agtr2(+) mice. The neurological deficit after MCA occlusion was also greater in Agtr2(-) mice than in Agtr2(+) mice. The decrease in surface cerebral blood flow after MCA occlusion was significantly exaggerated in the peripheral region of the MCA territory in Agtr2(-) mice. Superoxide production and NADPH oxidase activity were enhanced in the ischemic area of the brain in Agtr2(-) mice. An AT(1) receptor blocker, valsartan, at a nonhypotensive dose significantly inhibited the ischemic area, neurological deficit, and reduction of cerebral blood flow as well as superoxide production and NADPH oxidase activity in Agtr2(+) mice. These inhibitory actions of valsartan were weaker in Agtr2(-) mice.Conclusions-These results suggest that AT(2) receptor stimulation has a protective effect on ischemic brain lesions, at least partly through the modulation of cerebral blood flow and superoxide production.