Thöne-Reineke Christa, Steckelings Ulrike M, Unger Thomas
Centre for Cardiovascular Research/Institute for Pharmacology and Toxicology, Charité--Universitätsmedizin Berlin, Germany.
J Hypertens Suppl. 2006 Mar;24(1):S115-21. doi: 10.1097/01.hjh.0000220416.07235.37.
Stroke is a burden of modern civilization, causing death and disability. Nowadays it is universally accepted that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors or angiotensin II type 1 (AT1) receptor blockers (ARBs) can effectively decrease the incidence of stroke in patients at risk. Here, we summarize current knowledge concerning the molecular mechanisms of the beneficial effects of inhibition of the renin-angiotensin system in stroke, with an emphasis on mechanisms beyond blood pressure reduction; in particular, neuroprotection. All major clinical studies comparing the effectiveness of ARBs with placebo or other blood pressure decreasing drugs in stroke are mentioned and commented on. These clinical data are complemented by data from a selection of animal experiments pivotal for the understanding of neuroprotective actions of ARBs. Clinical studies have shown that ARBs can be superior to other antihypertensive drugs in the prevention of stroke, even if there are no differences in blood pressures. Findings from animal experiments suggest that the underlying mechanisms include not just inhibition of the detrimental peripheral and central actions of angiotensin II mediated by AT1-receptors, but also stimulation of unopposed angiotensin II type 2 (AT2) receptors that are upregulated in the area of ischaemia. ARBs have been proven to be effective in the prevention of stroke via mechanisms that are both dependent on and independent of the antihypertensive abilities of the drugs.
中风是现代文明的一大负担，会导致死亡和残疾。如今，人们普遍认为，通过血管紧张素转换酶抑制剂或1型血管紧张素II（AT1）受体阻滞剂（ARB）抑制肾素-血管紧张素系统，可以有效降低中风高危患者的中风发生率。在此，我们总结了目前关于抑制肾素-血管紧张素系统在中风中产生有益作用的分子机制的知识，重点是血压降低以外的机制；特别是神经保护作用。文中提及并评论了所有比较ARB与安慰剂或其他降压药物在中风方面有效性的主要临床研究。这些临床数据得到了一系列对理解ARB神经保护作用至关重要的动物实验数据的补充。临床研究表明，即使血压没有差异，ARB在预防中风方面也可能优于其他降压药物。动物实验结果表明，其潜在机制不仅包括抑制由AT1受体介导的血管紧张素II的有害外周和中枢作用，还包括刺激在缺血区域上调的未被拮抗的2型血管紧张素II（AT2）受体。ARB已被证明通过依赖和不依赖于药物降压能力的机制有效预防中风。
