Cardiovascular and Metabolism Disease Area, Novartis Institutes for BioMedical Research and Novartis Pharmaceuticals Corp., East Hanover, NJ, USA.
Hypertens Res. 2010 Apr;33(4):279-87. doi: 10.1038/hr.2010.19. Epub 2010 Mar 5.
The renin-angiotensin-aldosterone system (RAAS) has a central function in the regulation of blood pressure. Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation. As renin inhibition acts at the top of the RAAS cascade, this mechanism has been proposed to offer advantages over existing modes of RAAS blockade. The RAAS is also considered to be a major factor in the pathogenesis of many renal diseases, especially diabetic nephropathy (DN), the main cause of end-stage renal disease. Existing therapies to block the RAAS slow the progression of DN, but they do not halt the disease. Therefore, more effective modes of interventions are needed. Studies to determine the efficacy of aliskiren in human renal disease are in progress. This review summarizes in vivo studies in which the efficacy of aliskiren was tested in experimental models of renal disease, and presents in vitro studies that provide insights into the possible mechanisms by which aliskiren confers renoprotection in animals. These works are discussed in the framework of the intrarenal RAAS and suggest that aliskiren may act by unique renoprotective mechanisms.
肾素-血管紧张素-醛固酮系统（RAAS）在血压调节中具有核心功能。阿利克仑是首个被批准用于治疗高血压的直接肾素抑制剂，可在 RAAS 激活点阻断该系统。由于肾素抑制作用发生在 RAAS 级联反应的顶端，因此该机制被认为优于现有的 RAAS 阻断模式。RAAS 也被认为是许多肾脏疾病发病机制中的主要因素，尤其是糖尿病肾病（DN），这是终末期肾病的主要原因。现有的 RAAS 阻断疗法可减缓 DN 的进展，但并不能阻止该疾病。因此，需要更有效的干预模式。正在进行研究以确定阿利克仑在人类肾脏疾病中的疗效。本综述总结了在肾脏疾病的实验模型中测试阿利克仑疗效的体内研究，并介绍了提供有关阿利克仑在动物中发挥肾保护作用的可能机制的见解的体外研究。这些研究工作是在肾内 RAAS 的框架内进行讨论的，并表明阿利克仑可能通过独特的肾保护机制发挥作用。
