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左心室肥厚中的血管紧张素 AT2 受体。

The angiotensin AT2 receptor in left ventricular hypertrophy.

机构信息

Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, Berlin, Germany.

出版信息

J Hypertens. 2010 Sep;28 Suppl 1:S50-5. doi: 10.1097/01.hjh.0000388495.66330.63.

Abstract

Left ventricular hypertrophy (LVH) is considered a major predictor of cardiovascular morbidity and mortality. While it is unanimously accepted that the angiotensin AT1 receptor is involved in the pathogenesis of hypertension and LVH, the role of the AT2 receptor in LVH is still controversial. Most studies addressing the involvement of the AT2 receptor in LVH have been performed in genetically altered, either AT2 receptor-deficient or AT2 receptor-overexpressing mice. Unfortunately, this experimental approach turned out to yield highly controversial results with an almost equal number of studies supporting prohypertrophic or antihypertrophic or neutral effects of the AT2 receptor in LVH. Interestingly, in-vivo studies in wild-type animals using the AT2 receptor antagonist, PD123319, are less controversial and mainly revealed antigrowth effects of the AT2 receptor provided the study duration was sufficiently long. In the future, the novel non-peptide AT2 receptor agonist, compound 21, will allow the effects of the AT2 receptor in LVH to be studied by direct, selective AT2 receptor stimulation in vivo- a novel approach, which will hopefully help to overcome current controversies.

摘要

左心室肥厚(LVH)被认为是心血管发病率和死亡率的主要预测因素。虽然普遍认为血管紧张素 AT1 受体参与高血压和 LVH 的发病机制,但 AT2 受体在 LVH 中的作用仍存在争议。大多数关于 AT2 受体在 LVH 中作用的研究都是在基因改变的、AT2 受体缺陷或 AT2 受体过表达的小鼠中进行的。不幸的是,这种实验方法产生了极具争议的结果,几乎有同等数量的研究支持 AT2 受体在 LVH 中具有促肥厚、抗肥厚或中性作用。有趣的是,在使用 AT2 受体拮抗剂 PD123319 的野生型动物的体内研究中,结果的争议性较小,主要显示 AT2 受体的抗生长作用,只要研究持续时间足够长。未来,新型非肽 AT2 受体激动剂化合物 21 将允许通过直接、选择性的 AT2 受体刺激在体内研究 AT2 受体在 LVH 中的作用——这是一种新的方法,有望有助于克服当前的争议。

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