Epstein Benjamin J, Leonard Paul T, Shah Niren K
Department of Pharmacotherapy and Translational Research, University of Florida, PO Box 100487, Gainesville, FL 32610, USA.
Expert Rev Cardiovasc Ther. 2012 Jun;10(6):713-25. doi: 10.1586/erc.12.63.
Chronic renin-angiotensin-aldosterone system (RAAS) activation has far-reaching effects on cardiometabolic risk and is a substantial contributor to cardiovascular (CV) disease and renal dysfunction. The vascular effects of sustained RAAS activation are associated with hemodynamic imbalances, as well as inflammatory stimulation and prothrombotic processes that lead to fibrosis, endothelial dysfunction and cellular remodeling. RAAS inhibition therapies, which include the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and more recently, direct renin inhibitors, have been used in clinical practice for more than 30 years. Our understanding of how these drugs work, alone and in combination, has contributed to an expanding landscape of treatment options and established RAAS inhibition as essential for reducing the risk of CV and renal disease. This perspective provides a historical overview of how RAAS inhibitors have evolved to their present-day status and will discuss recently discovered functions for components of this complicated and powerful regulatory system.
慢性肾素-血管紧张素-醛固酮系统（RAAS）激活对心脏代谢风险具有深远影响，并且是心血管（CV）疾病和肾功能不全的重要促成因素。持续的RAAS激活所产生的血管效应与血流动力学失衡以及炎症刺激和促血栓形成过程相关，这些过程会导致纤维化、内皮功能障碍和细胞重塑。RAAS抑制疗法，包括使用血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂以及最近的直接肾素抑制剂，已在临床实践中使用了30多年。我们对这些药物单独使用及联合使用时作用机制的理解，促成了治疗选择范围的扩大，并确立了RAAS抑制对于降低CV和肾脏疾病风险的必要性。本观点文章提供了RAAS抑制剂如何发展至当前地位的历史概述，并将讨论这一复杂而强大的调节系统各组成部分最近发现的功能。
