Gene regulation and biophysiological significance of angiotensin type 2 receptor

血管紧张素受体(Ang)II的亚型有AT1-R和AT2-R两种，AT1-R介导了Ang II的大部分心血管作用，AT2-R在发育中胎儿的表达水平很高，而在成人心血管系统中的表达很低。AP2-R的表达可以受到与组织重塑或炎症相关的病理状态的调节。在衰竭的心脏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中重新表达，并抑制Ang II诱导的丝裂原信号或细胞外基质蛋白的合成，从而减弱组织重塑。一种极端的细胞生长抑制方式使细胞进入程序性细胞死亡，AT2-R也促进了AT2-R启动的细胞程序性死亡过程。心肌细胞或血管平滑肌特异性过表达AT2-R的小鼠对Ang II诱导的变时性或升压作用具有抑制作用，提示AT2-R在心脏起搏细胞活动或维持血管阻力中起作用。AT2-R还激活心血管和肾脏系统中的激动素/一氧化氮/cGMP系统，导致AT2-R介导的心脏保护、血管扩张和压力尿。AT2-R传递的这些效应主要是通过刺激蛋白酪氨酸或丝氨酸/苏氨酸磷酸酶而发挥作用的，这种作用依赖于胃肠道蛋白。AT2-R在人类心脏中的表达水平远高于啮齿类动物，AT2-R介导的作用可能会增强，尤其是在临床应用AT1-R拮抗剂后。

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.