Wolf Gunter
Department of Internal Medicine III, Friedrich-Schiller-University, Jena, Germany.
Front Biosci. 2008 May 1;13:4993-5005. doi: 10.2741/3058.
The renin-angiotensin-aldosterone system (RAAS) play a pivotal role in the progression of renal disease. The RAAS has become much more complex in recent years with the identification of novel peptides that exhibit biological activity. There are novel pathways of angiotensin II (ANG II) generation independent of angiotensin converting enzyme (ACE). ANG II bind to at least two different receptors and prorenin/renin also exerts pathophysiological effects through binding to specific receptor. ANG II itself has emerged as a multifunctional cytokine exhibiting many non-hemodynamic properties such as acting as a growth factor and profibrogenic and proinflammatory cytokine. These profibrogenic and proinflammatory effects are mediated by other factors such as transforming growth-factor beta (TGF-beta) and chemoattractants that are induced in the kidney by ANG II. Increased aldosterone levels contribute to renal injury, independent of blood pressure or ANG II. Numerous experimental and clinical studies have shown that ACE-inhibitors as well as AT1-receptor antagonists can prevent glomerulosclerosis and tubulointerstitial fibrosis. This review will highlight some of these novel insights into the RAAS in regards to renal injury.
肾素-血管紧张素-醛固酮系统（RAAS）在肾脏疾病进展中起关键作用。近年来，随着具有生物活性的新型肽的发现，RAAS变得更加复杂。存在不依赖血管紧张素转换酶（ACE）的血管紧张素II（ANG II）生成新途径。ANG II与至少两种不同受体结合，并且肾素原/肾素也通过与特定受体结合发挥病理生理作用。ANG II本身已成为一种多功能细胞因子，表现出许多非血流动力学特性，如作为生长因子以及促纤维化和促炎细胞因子。这些促纤维化和促炎作用由其他因子介导，如转化生长因子β（TGF-β）和由ANG II在肾脏中诱导产生的趋化因子。醛固酮水平升高导致肾损伤，与血压或ANG II无关。大量实验和临床研究表明，ACE抑制剂以及AT1受体拮抗剂可预防肾小球硬化和肾小管间质纤维化。本综述将重点介绍这些关于RAAS与肾损伤相关的新见解。
