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血管紧张素Ⅱ(AngⅡ)1型受体(AT_1-R)是G蛋白偶联受体家族成员之一,主要表达在细胞膜上,为7次跨膜结构蛋白。其活化与心血管疾病的发生发展密切相关。以往研究认为心肌组织及微循环局部产生的AngⅡ通过自分泌或旁分泌的方式激活AT_1-R从而引起心肌细胞肥大的发生发展。最近研究发现高血压产生的压力超负荷可不依赖AngⅡ直接激活AT_1-R,通过受体下游信号分子介导心肌损伤。而有关AT1-R如何参与容量负荷介导的心肌肥厚机制目前了解甚少。AT_1-R阻滞剂(ARB)通常可与AngⅡ竞争性拮抗,抑制AT_1-R活性发挥降压和靶器官的保护作用。而部分ARB不仅拮抗AngⅡ对AT_1-R的激活还可抑制压力超负荷对AT_1-R的激活,这种具有不依赖激动剂存在的受体抑制效应被定义为反向激动作用。综述AngⅡ依赖性和机械应力直接激活AT_1-R的研究进展,并讨论AT_1-R的拮抗和反向激动效应在心血管保护中的临床意义。
Angiotensin Ⅱ type 1 receptor (AT1-R) is a member of the G protein-coupled receptor family and is mainly expressed on the cell membrane, which is a seven-transmembrane structural protein. Its activation is closely related to the occurrence and development of cardiovascular diseases. In the past, it is thought that AngⅡ, which is produced locally by myocardial tissue and microcirculation, activates AT_1-R through autocrine or paracrine, which causes the occurrence and development of cardiomyocyte hypertrophy. Recent studies have found that pressure overload caused by hypertension can directly activate AT_1-R independent of AngⅡ, and mediate myocardial injury through signaling molecules downstream of the receptor. However, little is known about how AT1-R participates in capacity-load-mediated cardiac hypertrophy. AT1-R blockers (ARBs) usually antagonize Ang II competitively and inhibit AT1-R activity to exert antihypertensive and target organ protective effects. However, some ARBs not only antagonize the activation of AT1-R by AngⅡ, but also inhibit the activation of AT1-R by pressure overload. The inhibitory effect of this receptor with no agonist is defined as inverse agonism. This review summarizes the research progress of AT1-R activated by AngⅡ-dependent and mechanical stress, and discusses the clinical significance of AT1-R antagonism and inverse agonism in cardiovascular protection.