Angiotensin II Type 2 (AT2) Receptor Singnal and Cardiovascular Action

由于非肽配体的发现，血管紧张素受体（Angl II）被分为两个亚型（AT1-R和AT2-R）。AT1-R。介导angii的大部分心血管作用。AT2-R在发育中的肾脏中表达水平非常高。它在成人心血管系统中的表达非常低。AT2-R的表达可以通过与组织重塑或炎症相关的病理状态来调节。在心脏衰竭或血管损伤后的新生内膜形成中，AT2-R在间质区或新生内膜增殖的细胞中重新表达，对Ang ii诱导的有丝分裂原信号或细胞外基质蛋白的合成产生抑制作用，导致组织重构的衰减。细胞生长抑制的一种极端形式以程序性细胞死亡结束，这一过程由生长因子的退出启动，也被AT2-R增强。过度表达AT2-R的心肌细胞或血管平滑肌特异性小鼠显示抑制Ang ii诱导的变时或加压作用，提示AT2-R在心脏起搏器细胞活性和血管阻力维持中的作用。AT2-R也激活激肽/一氧化氮。氧化/cGMP系统在心血管和肾脏系统，在at2 - r介导的心脏保护，血管舒张和压力尿钠。这些作用由AT2-R传递，主要通过刺激蛋白酪氨酸或丝氨酸/苏氨酸磷酸酶以gi蛋白依赖的方式发挥作用。AT2-R在人类心脏中的表达水平远高于动物心脏，并且AT2-R介导的作用可能会增强，特别是临床应用AT1-R拮抗剂。因此，本文就AT2-R的表达调控、细胞定位、在心血管和肾脏疾病中的病理作用以及AT2-R刺激的药物治疗作用等方面进行综述。

Due to the discovery of nonpeptidic ligands the receptors for angiotensin (Angl II are classified into two subtypes (AT1-R and AT2-R). AT1-R. mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetlrs. Its expression is vefy low in the cardiovascular system of the adult. The expression of AT2-R can be modulated by pathological states associated with tissue remodeling or inflaimmation. In failing hearts or neointima fonnation after vascular injury, AT2-R is re-expressed in cells proliferating in interstitial regions or neointima and exerts an inhibitory effect on Ang II-induced mitogen signals or synthesis of extracellular matrix proteins, resulting in attenuation of the tissue remodeling. An extreme form of cell growth inhibition ends in programmed cell death, and this process, which is initiated by the withdrawal of growth factors, is also enhanced by AT2-R. Cardiac myocyte- or vascular smooth muscle-specific mice that overexpress AT2-R display an inhibition of Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells and the maintenance of vascular resistance. AT2-R also activates the kinin/nitric. oxide/cGMP system in the cardiovascular and renal systems, restnlting in AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects, transmitted by AT2-R, are mairily exerted by stimulation of protein tyrosine or serine/threonine phosphatases in a Gi-protein- dependent manner. The expression level of AT2-R is much higher in human hearts than in rodept hearts, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists. Thus, in this review, the regtilation of AT2-R expression, its cellular localization, its pathological role in cardiovascular and kidney ciseases, and phamlacotherapeutic effects of AT2-R stimulation are discussed.