National Institute of Science and Technology in Nanobiopharmaceutics, Department of Physiology and Biophysics, Federal University of Minas Gerais, Av. Antonio Carlos, 6627 - ICB - UFMG, 31270-901, Belo Horizonte, MG, Brazil.
Curr Hypertens Rep. 2014 Jun;16(6):433. doi: 10.1007/s11906-014-0433-0.
The renin-angiotensin system is an important component of the central and humoral mechanisms of blood pressure and hydro-electrolytic balance control. Angiotensin II is a key player of this system. Twenty-five years ago the first manuscripts describing the formation and actions of another peptide of the RAS, angiotensin-(1-7), were published. Since then several publications have shown that angiotensin-(1-7) is as pleiotropic as angiotensin II, influencing the functions of many organs and systems. The identification of the ACE homologue ACE2 and, a few years later, Mas, as a receptor for angiotensin-(1-7) contributed a great deal to establish this peptide as a key player of the RAS. Most of the actions of angiotensin-(1-7) are opposite to those described for angiotensin II. This has led to the concept of two arms of the RAS: one comprising ACE/AngII/AT1R and the other ACE2/Ang-(1-7)/Mas. More recently, we have described the identification of a novel component of the RAS, alamandine, which binds to the Mas-related G protein coupled receptor D. This peptide is formed by decarboxylation of the Asp residue of angiotensin-(1-7), leading to the formation of Ala as the N-terminal amino acid. Alternatively, it can be formed by hydrolysis of Ang A, by ACE2. Its effects include vasorelaxation, central effects similar to those produced by angiotensin-(1-7), blunting of isoproterenol-induced heart fibrosis, and anti-hypertensive action in SHR. The putative enzyme responsible for alamandine formation from angiotensin-(1-7) is under investigation. The identification of this novel component of the RAS opens new venues for understanding its physiological role and opens new putative therapeutic possibilities for treating cardiovascular diseases.
肾素-血管紧张素系统是血压和水盐平衡调控的中枢和体液机制的重要组成部分。血管紧张素 II 是该系统的关键因子。25 年前，描述肾素-血管紧张素系统另一种肽——血管紧张素-(1-7)形成和作用的首批论文发表。此后，多项研究表明血管紧张素-(1-7)与血管紧张素 II 一样具有多效性，影响许多器官和系统的功能。ACE 同工酶 ACE2 和几年后 Mas 被鉴定为血管紧张素-(1-7)的受体，这为将该肽确定为肾素-血管紧张素系统的关键因子做出了巨大贡献。血管紧张素-(1-7)的大多数作用与血管紧张素 II 描述的作用相反。这导致了肾素-血管紧张素系统的两个分支的概念：一个分支包括 ACE/血管紧张素 II/AT1R，另一个分支包括 ACE2/血管紧张素-(1-7)/Mas。最近，我们描述了肾素-血管紧张素系统的一个新成分——阿伐拉肽的鉴定，它与 Mas 相关的 G 蛋白偶联受体 D 结合。这种肽是由血管紧张素-(1-7)的 Asp 残基脱羧形成的，导致 Ala 作为 N 端氨基酸。或者，它可以通过 ACE2 水解 Ang A 形成。其作用包括血管舒张、与血管紧张素-(1-7)产生的中枢作用相似、减弱异丙肾上腺素诱导的心脏纤维化以及在 SHR 中的降压作用。负责从血管紧张素-(1-7)形成阿伐拉肽的假定酶正在研究中。该肾素-血管紧张素系统新成分的鉴定为理解其生理作用开辟了新的途径，并为治疗心血管疾病提供了新的潜在治疗可能性。
