Gene regulation and biophysiological significance of angiotensin type 2 receptor

血管紧张素（Ang） II的受体根据非肽配体的发现分为AT1-R和AT2-R两种亚型，AT1-R介导了Ang II的大部分心血管作用。AT2-R在发育中的胎儿中表达水平非常高，而在成人中，其在心血管系统中的表达水平非常低。AP2-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新内膜形成时，AT2-R在间质区或新内膜增殖的细胞中重新表达，对Angⅱ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方式导致细胞进入程序性死亡，其过程由生长因子的退出启动，AT2-R也增强了这一过程。心肌细胞或血管平滑肌特异性过表达AT2-R的小鼠对Ang ii诱导的变时或加压作用表现出抑制作用，提示AT2-R在心脏起搏器细胞活性或维持血管阻力方面的作用。AT2-R还激活心血管和肾脏系统中的激肽/一氧化氮/cGMP系统，从而产生AT2-R介导的心脏保护、血管舒张和压力尿。AT2-R传递的这些作用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啮齿类动物，并且AT2-R介导的作用可能会增强，特别是通过AT1-R拮抗剂的临床应用。

The receptors for angiotensin (Ang) II are classified into Iwo subtypes (AT1-R and AT2-R) by the discovery of non-peptidic ligands and AT1-R mediates most of the cardiovascular actions of Ang II.AT2-R is expressed at very high levels in the developing fetus, whereas in the adult its expression in the cardiovascular system is very low. The expression of AP2-R can be modulated by pathological states associated with tissue remodeling or inflammation. In failing hearts or neointima formation 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 way of cell growth inhibition directs cells into programmed cell death, and its process initiated by withdrawal of growth factors is also enhanced by AT2-R.Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal system, resulting in the AT2-R-mediated cardioprotection, vasodilation and pressure nairiuresis. These effects transmitted by AT2-R are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in Gi-protein dependent manner. The expression level of AT2-R is much higher in human hearts than in those of rodents, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists.