Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke.
Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke.
复制标题
血管紧张素-（1-7）对内皮素-1 诱导的缺血性中风的脑保护作用。
DOI：
10.1113/expphysiol.2011.058578
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发表时间：
2011-10
影响因子：
2.7
通讯作者：
Sumners C
中科院分区：
文献类型：
--
作者：
Mecca AP;Regenhardt RW;O'Connor TE;Joseph JP;Raizada MK;Katovich MJ;Sumners C
血管紧张素转换酶 2 (ACE2) 的激活、血管紧张素-(1-7) [Ang-(1-7)] 的产生和 Ang-(1-7) 受体 Mas 的刺激在各种外周心血管疾病中发挥有益作用，主要是通过其 1 型受体对抗血管紧张素 II 的有害作用。在这里，我们考虑了 Ang-(1-7) 可能对脑缺血性中风引起的中枢神经系统损伤和神经功能缺损发挥有益作用的可能性。我们确定了中枢给予 Ang-(1-7) 或药物激活 ACE2 对内皮素-1 (ET-1) 诱导的大脑中动脉闭塞 (MCAO)（一种脑缺血模型）引起的脑损伤和行为缺陷的影响。本研究的结果表明，在 ET-1 诱导的 MCAO 之前和之后，脑室内输注 Ang-(1-7) 或 ACE2 激活剂二米嗪乙酰酯 (DIZE) 可显着减轻脑梗死面积和损伤后 72 小时测量到的神经功能缺损。 Ang-(1-7) 和 DIZE 的这些有益作用可通过侧脑室内同时给予 Mas 受体抑制剂 A-779 来逆转。 Ang-(1-7) 和 DIZE 治疗均未改变 ET-1 引起的脑血流量减少。最后，脑室内给予 Ang-(1-7) 显着降低了 ET-1 诱导的 MCAO 后发生的脑梗塞内诱导型一氧化氮合酶 mRNA 表达的增加。这是首次证明 ACE2-Ang-(1-7)-Mas 轴在缺血性中风期间具有脑保护作用，并表明 Ang-(1-7) 保护作用的机制包括减弱诱导型一氧化氮合酶的表达。
Activation of angiotensin-converting enzyme 2 (ACE2), production of angiotensin-(1–7) [Ang-(1–7)] and stimulation of the Ang-(1–7) receptor Mas exert beneficial actions in various peripheral cardiovascular diseases, largely through opposition of the deleterious effects of angiotensin II via its type 1 receptor. Here we considered the possibility that Ang-(1–7) may exert beneficial effects against CNS damage and neurological deficits produced by cerebral ischaemic stroke. We determined the effects of central administration of Ang-(1–7) or pharmacological activation of ACE2 on the cerebral damage and behavioural deficits elicited by endothelin-1 (ET-1)-induced middle cerebral artery occlusion (MCAO), a model of cerebral ischaemia. The results of the present study demonstrated that intracerebroventricular infusion of either Ang-(1–7) or an ACE2 activator, diminazine aceturate (DIZE), prior to and following ET-1-induced MCAO significantly attenuated the cerebral infarct size and neurological deficits measured 72 h after the insult. These beneficial actions of Ang-(1–7) and DIZE were reversed by co-intracerebroventricular administration of the Mas receptor inhibitor, A-779. Neither the Ang-(1–7) nor the DIZE treatments altered the reduction in cerebral blood flow elicited by ET-1. Lastly, intracerebroventricular administration of Ang-(1–7) significantly reduced the increase in inducible nitric oxide synthase mRNA expression within the cerebral infarct that occurs following ET-1-induced MCAO. This is the first demonstration of cerebroprotective properties of the ACE2–Ang-(1–7)–Mas axis during ischaemic stroke, and suggests that the mechanism of the Ang-(1–7) protective action includes blunting of inducible nitric oxide synthase expression.
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影响因子：
8.3
作者：
Kagiyama, T;Glushakov, AV;Martynyuk, AE
通讯作者：
Martynyuk, AE
影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
7.3
作者：
Cao, W.;Shah, H. P.;Martynyuk, A. E.
通讯作者：
Martynyuk, A. E.
影响因子：
7.3
作者：
Parmentier, S;Böhme, GA;Plotkine, M
通讯作者：
Plotkine, M