Angiotensin II type 1 receptors in cerebral ischaemia-reperfusion: initiation of inflammation.
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.
Schulz
Rainer
R
Institute for Pathophysiology, University of Duisburg-Essen, Essen, Germany. Rainer_Schulz@uni-essen.de
Heusch
Gerd
G
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D002545:Brain Ischemia / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005609:Free Radicals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology*; D009569:Nitric Oxide / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D047228:Angiotensin II Type 1 Receptor Blockers; D005609:Free Radicals; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide