Oprisiu-Fournier Roxana, Faure Sébastien, Mazouz Hakim, Boutitie Florent, Serot Jean-Marie, Achard Jean-Michel, Godefroy Olivier, Hanon Olivier, Temmar Mohammed, Albu Adriana, Strandgaard Svend, Wang Jiguang, Black Sandra E, Fournier Albert
Geriatrics Department University Hospital, Amiens, France.
Expert Rev Neurother. 2009 Sep;9(9):1289-305. doi: 10.1586/ern.09.88.
First, an update of the vascular systemic and tissue renin-angiotensin-aldosterone system is provided to explain how it is regulated at the systemic and tissue levels, and how many angiotensin peptides and receptors can be modulated by the various antihypertensive drugs. Second, experimental data is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers and angiotensin-converting enzyme inhibitors, because they increase activation of angiotensin AT2 and AT4 receptors. Indeed, these trigger brain anti-ischemic mechanisms by favouring cerebral blood flow (angiogenesis and recruitment of pre-existing collateral circulation, specifically in the ischemic brain where AT2 receptors are overexpressed) or by directly increasing neuronal resistance to anoxia. Third, we review most of the large primary and secondary stroke prevention trials as well as the ACCESS acute stroke trial in which antihypertensive drugs were evaluated. With the exception of the secondary stroke prevention trial PRoFESS, most trials support the hypothesis that angiotensin II-increasing drugs confer specific blood pressure-independent brain ischemia protection when compared with angiotensin II-decreasing drugs or placebo. A careful analysis of the PRoFESS trial, however, reveals study design limitations, the main one being that diastolic BP (<80 mmHg) in the first month post-stroke may have been too low in at least one third of the population with baseline systolic blood pressure less than 130 mmHg, because a high dose of telmisartan was given after a very short post-stroke delay (median 15 days) without discontinuation of the baseline antihypertensive treatment.
首先，对血管系统和组织肾素 - 血管紧张素 - 醛固酮系统进行更新，以解释其在系统和组织水平上是如何被调节的，以及各种降压药物可以调节多少种血管紧张素肽和受体。其次，给出实验数据以支持这样的假说：增加血管紧张素II形成的降压药物，如利尿剂、AT1受体阻滞剂和二氢吡啶类药物，可能比减少血管紧张素II形成的降压药物，如β受体阻滞剂和血管紧张素转换酶抑制剂，具有更强的脑抗缺血作用，因为它们增加了血管紧张素AT2和AT4受体的激活。事实上，这些药物通过促进脑血流量（血管生成和募集预先存在的侧支循环，特别是在缺血脑中AT2受体过度表达的区域）或直接增加神经元对缺氧的耐受性来触发脑抗缺血机制。第三，我们回顾了大多数评估降压药物的大型一级和二级卒中预防试验以及ACCESS急性卒中试验。除了二级卒中预防试验PRoFESS外，大多数试验支持这样的假说：与减少血管紧张素II的药物或安慰剂相比，增加血管紧张素II的药物可提供独立于血压的特定脑缺血保护作用。然而，对PRoFESS试验的仔细分析揭示了研究设计的局限性，主要问题是在至少三分之一基线收缩压低于130 mmHg的人群中，卒中后第一个月的舒张压（<80 mmHg）可能过低，因为在卒中后很短的延迟时间（中位数15天）后给予了高剂量的替米沙坦，且未停用基线降压治疗。
