Schulz Rainer, Heusch Gerd
Institute for Pathophysiology, University of Duisburg-Essen, Essen, Germany.
J Hypertens Suppl. 2006 Mar;24(1):S123-9. doi: 10.1097/01.hjh.0000220417.01397.6a.
Cerebral ischaemia-reperfusion injury is associated with an inflammatory response, with contributions from leucocytes and microglia. Formation of free radicals and nitric oxide contributes to the development of cerebral infarction and of the neurological deficit that follows transient focal ischaemia. The circulating and cerebral renin-angiotensin systems contribute, via stimulation of the angiotensin II (Ang II) types 1 (AT1) and 2 receptors, to the initiation or progression of inflammatory processes, and blockade of AT1-receptors prevents irreversible tissue injury and improves outcome from stroke in animal experiments. Such cerebral protection can be achieved even when treatment is initiated hours after established reperfusion. Blockade of AT1-receptors also reduces the incidence of stroke and cardiovascular mortality associated with stroke in patients; however, the mechanisms underlying the prevention of stroke by AT1-receptor blockade in patients remain to be elucidated. In this review we summarize the existing experimental and clinical data demonstrating that the renin-angiotensin system contributes to the inflammation and subsequent irreversible injury after cerebral ischaemia-reperfusion. We conclude that AT1-receptor blockade reduces cerebral ischaemia-reperfusion injury in part by attenuating inflammatory processes.
脑缺血再灌注损伤与炎症反应相关，涉及白细胞和小胶质细胞。自由基和一氧化氮的形成促成了脑梗死的发展以及短暂性局灶性缺血后出现的神经功能缺损。循环和脑肾素 - 血管紧张素系统通过刺激1型（AT1）和2型血管紧张素II（Ang II）受体，促进炎症过程的启动或进展，而阻断AT1受体可防止不可逆的组织损伤，并改善动物实验中的中风结局。即使在再灌注数小时后开始治疗，也能实现这种脑保护作用。阻断AT1受体还可降低患者中风的发生率以及与中风相关的心血管死亡率；然而，AT1受体阻断预防患者中风的潜在机制仍有待阐明。在本综述中，我们总结了现有的实验和临床数据，这些数据表明肾素 - 血管紧张素系统促成了脑缺血再灌注后的炎症反应及随后的不可逆损伤。我们得出结论，AT1受体阻断部分通过减轻炎症过程来减少脑缺血再灌注损伤。
